<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2025 Workiva-->
<!--r:b6cc3e8e-84bc-4fd0-9adf-4dff7e921e19,g:ab2d82f3-dc5b-49e1-963c-ff74e7119bbd-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://macrogenics.com/role/CONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS" xlink:type="simple" xlink:href="mgnx-20250930.xsd#CONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/CONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_c1ec306b-9a58-44d3-a537-ffe370cb8665" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_6242aab1-b1b9-431b-95b9-eac0590fc5ff" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_c1ec306b-9a58-44d3-a537-ffe370cb8665" xlink:to="loc_us-gaap_StatementTable_6242aab1-b1b9-431b-95b9-eac0590fc5ff" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_239522e0-ec63-46c6-a09a-1ed1e64f7414" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_6242aab1-b1b9-431b-95b9-eac0590fc5ff" xlink:to="loc_srt_ProductOrServiceAxis_239522e0-ec63-46c6-a09a-1ed1e64f7414" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_239522e0-ec63-46c6-a09a-1ed1e64f7414_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_239522e0-ec63-46c6-a09a-1ed1e64f7414" xlink:to="loc_srt_ProductsAndServicesDomain_239522e0-ec63-46c6-a09a-1ed1e64f7414_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_80f3c27f-37af-49fa-9c14-784b1a7763ba" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_239522e0-ec63-46c6-a09a-1ed1e64f7414" xlink:to="loc_srt_ProductsAndServicesDomain_80f3c27f-37af-49fa-9c14-784b1a7763ba" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueFromCollaborativeAgreementsMember_6ed493ec-ea1e-4706-b36b-4d622af15b8e" xlink:href="mgnx-20250930.xsd#mgnx_RevenueFromCollaborativeAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_80f3c27f-37af-49fa-9c14-784b1a7763ba" xlink:to="loc_mgnx_RevenueFromCollaborativeAgreementsMember_6ed493ec-ea1e-4706-b36b-4d622af15b8e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_d7a4a57d-f176-4db3-983f-920f7209e8e1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_80f3c27f-37af-49fa-9c14-784b1a7763ba" xlink:to="loc_us-gaap_ProductMember_d7a4a57d-f176-4db3-983f-920f7209e8e1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ContractManufacturingMember_635ca297-3841-47fd-b406-9a5d0747669b" xlink:href="mgnx-20250930.xsd#mgnx_ContractManufacturingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_80f3c27f-37af-49fa-9c14-784b1a7763ba" xlink:to="loc_mgnx_ContractManufacturingMember_635ca297-3841-47fd-b406-9a5d0747669b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GovernmentContractMember_cd252795-df1c-4fc1-abee-e7a0f782bb77" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GovernmentContractMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_80f3c27f-37af-49fa-9c14-784b1a7763ba" xlink:to="loc_us-gaap_GovernmentContractMember_cd252795-df1c-4fc1-abee-e7a0f782bb77" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_86786e0b-dbf7-4f38-8034-88a1b3d9996e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_6242aab1-b1b9-431b-95b9-eac0590fc5ff" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_86786e0b-dbf7-4f38-8034-88a1b3d9996e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_86786e0b-dbf7-4f38-8034-88a1b3d9996e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_86786e0b-dbf7-4f38-8034-88a1b3d9996e" xlink:to="loc_us-gaap_SegmentDomain_86786e0b-dbf7-4f38-8034-88a1b3d9996e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_baec4196-760f-4e2c-975f-09109b498688" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_86786e0b-dbf7-4f38-8034-88a1b3d9996e" xlink:to="loc_us-gaap_SegmentDomain_baec4196-760f-4e2c-975f-09109b498688" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_MainSegmentMember_8a876a56-75a9-4fef-9ed8-3743a361c2fc" xlink:href="mgnx-20250930.xsd#mgnx_MainSegmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_baec4196-760f-4e2c-975f-09109b498688" xlink:to="loc_mgnx_MainSegmentMember_8a876a56-75a9-4fef-9ed8-3743a361c2fc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesAbstract_9902a9ad-9da3-4cd9-ac21-bb9076b88e1e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenuesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c1ec306b-9a58-44d3-a537-ffe370cb8665" xlink:to="loc_us-gaap_RevenuesAbstract_9902a9ad-9da3-4cd9-ac21-bb9076b88e1e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_3d5c223b-b738-46f3-b94f-bfda0662465a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesAbstract_9902a9ad-9da3-4cd9-ac21-bb9076b88e1e" xlink:to="loc_us-gaap_Revenues_3d5c223b-b738-46f3-b94f-bfda0662465a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpensesAbstract_44ab1585-1a6a-485f-99de-0b5083af93e0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostsAndExpensesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c1ec306b-9a58-44d3-a537-ffe370cb8665" xlink:to="loc_us-gaap_CostsAndExpensesAbstract_44ab1585-1a6a-485f-99de-0b5083af93e0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_e192ac5a-4b4e-4010-9622-d5ada97056e3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_44ab1585-1a6a-485f-99de-0b5083af93e0" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_e192ac5a-4b4e-4010-9622-d5ada97056e3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CostOfManufacturingServices_20a7e925-ad1c-4733-b8ca-a64b9a75fc47" xlink:href="mgnx-20250930.xsd#mgnx_CostOfManufacturingServices"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_44ab1585-1a6a-485f-99de-0b5083af93e0" xlink:to="loc_mgnx_CostOfManufacturingServices_20a7e925-ad1c-4733-b8ca-a64b9a75fc47" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_df8346e6-4bf5-4d59-a57f-7d116d745e78" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_44ab1585-1a6a-485f-99de-0b5083af93e0" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_df8346e6-4bf5-4d59-a57f-7d116d745e78" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_f87a23da-79f4-469a-af0e-49d61278e125" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_44ab1585-1a6a-485f-99de-0b5083af93e0" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_f87a23da-79f4-469a-af0e-49d61278e125" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_5d01c54b-80d6-453b-99e4-5dd1b72cac6a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostsAndExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_44ab1585-1a6a-485f-99de-0b5083af93e0" xlink:to="loc_us-gaap_CostsAndExpenses_5d01c54b-80d6-453b-99e4-5dd1b72cac6a" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_d48ab502-7937-4252-8313-18ee61cc3514" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_44ab1585-1a6a-485f-99de-0b5083af93e0" xlink:to="loc_us-gaap_OperatingIncomeLoss_d48ab502-7937-4252-8313-18ee61cc3514" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncome_4b88181b-75df-4fe0-944a-842284f91c28" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherNonoperatingIncome"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_44ab1585-1a6a-485f-99de-0b5083af93e0" xlink:to="loc_us-gaap_OtherNonoperatingIncome_4b88181b-75df-4fe0-944a-842284f91c28" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpense_7feef217-7be6-4989-a195-18d3269f4644" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InterestExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_44ab1585-1a6a-485f-99de-0b5083af93e0" xlink:to="loc_us-gaap_InterestExpense_7feef217-7be6-4989-a195-18d3269f4644" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_6e40d117-c7e5-4ea5-a76c-a77cdc4d6735" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_44ab1585-1a6a-485f-99de-0b5083af93e0" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_6e40d117-c7e5-4ea5-a76c-a77cdc4d6735" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_9d9f05a5-d999-4092-ab5a-67fcb24d3f69" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_44ab1585-1a6a-485f-99de-0b5083af93e0" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_9d9f05a5-d999-4092-ab5a-67fcb24d3f69" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_a06badf5-7926-4095-9d5c-6852f3dbd85c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_44ab1585-1a6a-485f-99de-0b5083af93e0" xlink:to="loc_us-gaap_NetIncomeLoss_a06badf5-7926-4095-9d5c-6852f3dbd85c" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract_fe461d09-41d1-4173-86cf-a413f8098c48" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c1ec306b-9a58-44d3-a537-ffe370cb8665" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract_fe461d09-41d1-4173-86cf-a413f8098c48" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_687a352a-454d-4139-9545-c073594f437b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract_fe461d09-41d1-4173-86cf-a413f8098c48" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_687a352a-454d-4139-9545-c073594f437b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_b20e2f65-5c3e-4aa8-a4db-3ef1d20ae2d3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c1ec306b-9a58-44d3-a537-ffe370cb8665" xlink:to="loc_us-gaap_ComprehensiveIncomeNetOfTax_b20e2f65-5c3e-4aa8-a4db-3ef1d20ae2d3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasicAbstract_3addfa11-9aef-4736-91d2-6c882a370b9f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersBasicAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c1ec306b-9a58-44d3-a537-ffe370cb8665" xlink:to="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasicAbstract_3addfa11-9aef-4736-91d2-6c882a370b9f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasic_94081362-5eb4-4855-a37c-6aad642c7d1a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EarningsPerShareBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasicAbstract_3addfa11-9aef-4736-91d2-6c882a370b9f" xlink:to="loc_us-gaap_EarningsPerShareBasic_94081362-5eb4-4855-a37c-6aad642c7d1a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_b49b2198-7aa4-4d69-b5d7-5da9bc04a0b9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasicAbstract_3addfa11-9aef-4736-91d2-6c882a370b9f" xlink:to="loc_us-gaap_EarningsPerShareDiluted_b49b2198-7aa4-4d69-b5d7-5da9bc04a0b9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasicAbstract_388701e0-58c8-4c67-a18d-f0ad693fbd8d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasicAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c1ec306b-9a58-44d3-a537-ffe370cb8665" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasicAbstract_388701e0-58c8-4c67-a18d-f0ad693fbd8d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_74251950-2438-4f54-acb4-87134dda24d8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasicAbstract_388701e0-58c8-4c67-a18d-f0ad693fbd8d" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_74251950-2438-4f54-acb4-87134dda24d8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_cfca2d9a-65a4-4733-9202-52251f258d39" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasicAbstract_388701e0-58c8-4c67-a18d-f0ad693fbd8d" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_cfca2d9a-65a4-4733-9202-52251f258d39" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/CONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY" xlink:type="simple" xlink:href="mgnx-20250930.xsd#CONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/CONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_b1906a03-4371-4664-84c6-edfbbf7a465b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_f1eb2140-e019-42b5-815a-5a7fcfae996e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_b1906a03-4371-4664-84c6-edfbbf7a465b" xlink:to="loc_us-gaap_StatementTable_f1eb2140-e019-42b5-815a-5a7fcfae996e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_727d1a1a-e1fd-4c06-8e04-ddda81588e98" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_f1eb2140-e019-42b5-815a-5a7fcfae996e" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_727d1a1a-e1fd-4c06-8e04-ddda81588e98" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_727d1a1a-e1fd-4c06-8e04-ddda81588e98_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_727d1a1a-e1fd-4c06-8e04-ddda81588e98" xlink:to="loc_us-gaap_EquityComponentDomain_727d1a1a-e1fd-4c06-8e04-ddda81588e98_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_ad7897a1-94e5-45cb-bede-c78e96706dfa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_727d1a1a-e1fd-4c06-8e04-ddda81588e98" xlink:to="loc_us-gaap_EquityComponentDomain_ad7897a1-94e5-45cb-bede-c78e96706dfa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_5bad7175-d91b-4989-9ccf-202e07bca35f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_ad7897a1-94e5-45cb-bede-c78e96706dfa" xlink:to="loc_us-gaap_CommonStockMember_5bad7175-d91b-4989-9ccf-202e07bca35f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_6e5481c4-d862-4b3e-b127-af8fe1b2813a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_ad7897a1-94e5-45cb-bede-c78e96706dfa" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_6e5481c4-d862-4b3e-b127-af8fe1b2813a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_481d1788-4ea3-47d4-b895-ac060258fdb6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_ad7897a1-94e5-45cb-bede-c78e96706dfa" xlink:to="loc_us-gaap_RetainedEarningsMember_481d1788-4ea3-47d4-b895-ac060258fdb6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AociIncludingPortionAttributableToNoncontrollingInterestMember_716a2cbf-63f7-461f-bfde-082c61fa5dc5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AociIncludingPortionAttributableToNoncontrollingInterestMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_ad7897a1-94e5-45cb-bede-c78e96706dfa" xlink:to="loc_us-gaap_AociIncludingPortionAttributableToNoncontrollingInterestMember_716a2cbf-63f7-461f-bfde-082c61fa5dc5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_df5a593d-e059-41d2-ab9d-7b13bef8f684" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_b1906a03-4371-4664-84c6-edfbbf7a465b" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_df5a593d-e059-41d2-ab9d-7b13bef8f684" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesIssued_55f09426-c407-42b3-99dc-55c7e1ac7b00" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_df5a593d-e059-41d2-ab9d-7b13bef8f684" xlink:to="loc_us-gaap_SharesIssued_55f09426-c407-42b3-99dc-55c7e1ac7b00" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_a404ccb9-479d-4e0a-93e9-e386bc021de5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_df5a593d-e059-41d2-ab9d-7b13bef8f684" xlink:to="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_a404ccb9-479d-4e0a-93e9-e386bc021de5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_671a27e8-f137-42b8-b250-25d541aa839f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_df5a593d-e059-41d2-ab9d-7b13bef8f684" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_671a27e8-f137-42b8-b250-25d541aa839f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_StockIssuedDuringPeriodSharesStockPlanActivity_fb6c2178-9c87-4f6c-9e5a-29e50e52368c" xlink:href="mgnx-20250930.xsd#mgnx_StockIssuedDuringPeriodSharesStockPlanActivity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_df5a593d-e059-41d2-ab9d-7b13bef8f684" xlink:to="loc_mgnx_StockIssuedDuringPeriodSharesStockPlanActivity_fb6c2178-9c87-4f6c-9e5a-29e50e52368c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockGrantedDuringPeriodValueSharebasedCompensation_11287991-955e-46ab-be14-52502f633d46" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockGrantedDuringPeriodValueSharebasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_df5a593d-e059-41d2-ab9d-7b13bef8f684" xlink:to="loc_us-gaap_StockGrantedDuringPeriodValueSharebasedCompensation_11287991-955e-46ab-be14-52502f633d46" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_StockIssuedDuringPeriodValueStockPlanActivity_9ba7e5b8-cf7c-471a-9428-d17c0bccf4ed" xlink:href="mgnx-20250930.xsd#mgnx_StockIssuedDuringPeriodValueStockPlanActivity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_df5a593d-e059-41d2-ab9d-7b13bef8f684" xlink:to="loc_mgnx_StockIssuedDuringPeriodValueStockPlanActivity_9ba7e5b8-cf7c-471a-9428-d17c0bccf4ed" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrealizedGainLossOnInvestments_a812edb6-6970-4bdf-84b4-4d26dc4cf68d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_UnrealizedGainLossOnInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_df5a593d-e059-41d2-ab9d-7b13bef8f684" xlink:to="loc_us-gaap_UnrealizedGainLossOnInvestments_a812edb6-6970-4bdf-84b4-4d26dc4cf68d" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_bb5a97fc-6cc3-43b3-ad47-f0119c3c4c44" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_df5a593d-e059-41d2-ab9d-7b13bef8f684" xlink:to="loc_us-gaap_NetIncomeLoss_bb5a97fc-6cc3-43b3-ad47-f0119c3c4c44" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesIssued_f97db85c-9780-4b45-ac02-2fb93b88034a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharesIssued"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_7c662c4e-1cb2-4c48-bc44-19eb8262132d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/FairValueofFinancialInstrumentsDetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#FairValueofFinancialInstrumentsDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/FairValueofFinancialInstrumentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_79c45c94-38f9-4b70-98c4-eb387bcf0766" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_92be119a-61fa-41bb-b8b4-7b6c61a24aae" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_79c45c94-38f9-4b70-98c4-eb387bcf0766" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_92be119a-61fa-41bb-b8b4-7b6c61a24aae" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_52475b58-6326-4f1e-acf4-92d2bf2dda08" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_92be119a-61fa-41bb-b8b4-7b6c61a24aae" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_52475b58-6326-4f1e-acf4-92d2bf2dda08" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_52475b58-6326-4f1e-acf4-92d2bf2dda08_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_52475b58-6326-4f1e-acf4-92d2bf2dda08" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_52475b58-6326-4f1e-acf4-92d2bf2dda08_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_d245aea2-0715-4125-b2d3-37c5097ab6c6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_52475b58-6326-4f1e-acf4-92d2bf2dda08" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_d245aea2-0715-4125-b2d3-37c5097ab6c6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_0b3f75a9-7e53-462e-ac6f-5a16c9390749" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_d245aea2-0715-4125-b2d3-37c5097ab6c6" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_0b3f75a9-7e53-462e-ac6f-5a16c9390749" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByAssetClassAxis_09b586f9-13e5-4f70-9dd1-9fe1dc7c3423" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueByAssetClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_92be119a-61fa-41bb-b8b4-7b6c61a24aae" xlink:to="loc_us-gaap_FairValueByAssetClassAxis_09b586f9-13e5-4f70-9dd1-9fe1dc7c3423" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_09b586f9-13e5-4f70-9dd1-9fe1dc7c3423_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_09b586f9-13e5-4f70-9dd1-9fe1dc7c3423" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_09b586f9-13e5-4f70-9dd1-9fe1dc7c3423_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_daff8c6c-ad23-4994-93d7-ccaf768f694d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_09b586f9-13e5-4f70-9dd1-9fe1dc7c3423" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_daff8c6c-ad23-4994-93d7-ccaf768f694d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_1d0230b0-bbc9-48e5-8b37-88b628006337" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_daff8c6c-ad23-4994-93d7-ccaf768f694d" xlink:to="loc_us-gaap_MoneyMarketFundsMember_1d0230b0-bbc9-48e5-8b37-88b628006337" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_41584ab1-a5c7-42eb-81b0-d8269cb9b921" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_daff8c6c-ad23-4994-93d7-ccaf768f694d" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_41584ab1-a5c7-42eb-81b0-d8269cb9b921" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_91700e0d-295e-498b-9019-dff07071a28d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_daff8c6c-ad23-4994-93d7-ccaf768f694d" xlink:to="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_91700e0d-295e-498b-9019-dff07071a28d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_25211c37-6d67-47a9-bfde-485fd2653897" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_daff8c6c-ad23-4994-93d7-ccaf768f694d" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_25211c37-6d67-47a9-bfde-485fd2653897" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_b4dfd720-da0e-42fe-bdc3-d207ada91c6e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_92be119a-61fa-41bb-b8b4-7b6c61a24aae" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_b4dfd720-da0e-42fe-bdc3-d207ada91c6e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_b4dfd720-da0e-42fe-bdc3-d207ada91c6e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_b4dfd720-da0e-42fe-bdc3-d207ada91c6e" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_b4dfd720-da0e-42fe-bdc3-d207ada91c6e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_29f70449-fedc-4fd1-a155-4a9180f61284" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_b4dfd720-da0e-42fe-bdc3-d207ada91c6e" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_29f70449-fedc-4fd1-a155-4a9180f61284" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_eed13964-f46e-4223-90bf-8a28ef1acd8b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_29f70449-fedc-4fd1-a155-4a9180f61284" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_eed13964-f46e-4223-90bf-8a28ef1acd8b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_1d02421b-0d1b-46b1-ab8b-47dea20db3e2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_29f70449-fedc-4fd1-a155-4a9180f61284" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_1d02421b-0d1b-46b1-ab8b-47dea20db3e2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosureAbstract_67aacc43-03d7-4fcd-bb1e-6490bb4cca86" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_79c45c94-38f9-4b70-98c4-eb387bcf0766" xlink:to="loc_us-gaap_AssetsFairValueDisclosureAbstract_67aacc43-03d7-4fcd-bb1e-6490bb4cca86" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_242c9a08-7737-4a0f-8cc8-9d42a6b3215f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_67aacc43-03d7-4fcd-bb1e-6490bb4cca86" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_242c9a08-7737-4a0f-8cc8-9d42a6b3215f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_ad54ec2e-9f02-4e26-9a8a-6da1cf5a3987" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_67aacc43-03d7-4fcd-bb1e-6490bb4cca86" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_ad54ec2e-9f02-4e26-9a8a-6da1cf5a3987" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_3dcb22f9-7fbf-4b4f-9122-dacd623cb01e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_67aacc43-03d7-4fcd-bb1e-6490bb4cca86" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_3dcb22f9-7fbf-4b4f-9122-dacd623cb01e" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/MarketableSecuritiesDetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#MarketableSecuritiesDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/MarketableSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_96cdca0a-d213-4afd-9401-a87536151572" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_f6ced04f-d622-43ef-87f4-6ecd664acf3a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_96cdca0a-d213-4afd-9401-a87536151572" xlink:to="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_f6ced04f-d622-43ef-87f4-6ecd664acf3a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_a528b90f-ef50-4021-8aad-43859b9182d0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_f6ced04f-d622-43ef-87f4-6ecd664acf3a" xlink:to="loc_us-gaap_FinancialInstrumentAxis_a528b90f-ef50-4021-8aad-43859b9182d0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_a528b90f-ef50-4021-8aad-43859b9182d0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_a528b90f-ef50-4021-8aad-43859b9182d0" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_a528b90f-ef50-4021-8aad-43859b9182d0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_c23c7924-daaf-4545-9117-18a3f4f05840" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_a528b90f-ef50-4021-8aad-43859b9182d0" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_c23c7924-daaf-4545-9117-18a3f4f05840" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_42738485-e59f-4839-9a32-01f1abd0d13c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_c23c7924-daaf-4545-9117-18a3f4f05840" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_42738485-e59f-4839-9a32-01f1abd0d13c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_d07964dc-33ec-4585-99a4-865ac2eb3953" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_c23c7924-daaf-4545-9117-18a3f4f05840" xlink:to="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_d07964dc-33ec-4585-99a4-865ac2eb3953" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_d932df24-4a66-4f9f-a9ec-7e63332038ed" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_c23c7924-daaf-4545-9117-18a3f4f05840" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_d932df24-4a66-4f9f-a9ec-7e63332038ed" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_ba7bb4ab-30de-4c42-b1fb-6878048fc172" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_96cdca0a-d213-4afd-9401-a87536151572" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_ba7bb4ab-30de-4c42-b1fb-6878048fc172" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_3be41b27-da2b-4acd-ae02-d8686bcbf9e7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_96cdca0a-d213-4afd-9401-a87536151572" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_3be41b27-da2b-4acd-ae02-d8686bcbf9e7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_fbe661bc-a5b4-473d-8db0-8327134a4961" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_96cdca0a-d213-4afd-9401-a87536151572" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_fbe661bc-a5b4-473d-8db0-8327134a4961" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_abff1c85-59a7-422b-a43c-6f3af0cfd398" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_96cdca0a-d213-4afd-9401-a87536151572" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_abff1c85-59a7-422b-a43c-6f3af0cfd398" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RoyaltyMonetizationArrangementNarrativeDetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#RoyaltyMonetizationArrangementNarrativeDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RoyaltyMonetizationArrangementNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_41b28c44-1a88-4f52-b2cd-58c21d18711a" xlink:href="mgnx-20250930.xsd#mgnx_LiabilityRelatedToFutureRoyaltyLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_LiabilityRelatedToFutureRoyaltyTable_bc0b79c0-d22a-438c-9dcc-f560d84c6d65" xlink:href="mgnx-20250930.xsd#mgnx_LiabilityRelatedToFutureRoyaltyTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_41b28c44-1a88-4f52-b2cd-58c21d18711a" xlink:to="loc_mgnx_LiabilityRelatedToFutureRoyaltyTable_bc0b79c0-d22a-438c-9dcc-f560d84c6d65" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_a20c2de5-52d8-4f86-8e18-31afd7a3cfb3" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyTable_bc0b79c0-d22a-438c-9dcc-f560d84c6d65" xlink:to="loc_srt_CounterpartyNameAxis_a20c2de5-52d8-4f86-8e18-31afd7a3cfb3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a20c2de5-52d8-4f86-8e18-31afd7a3cfb3_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_a20c2de5-52d8-4f86-8e18-31afd7a3cfb3" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a20c2de5-52d8-4f86-8e18-31afd7a3cfb3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_e42a40d8-c754-4256-9ff8-bbde24390791" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_a20c2de5-52d8-4f86-8e18-31afd7a3cfb3" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_e42a40d8-c754-4256-9ff8-bbde24390791" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_SagardHealthcarePartnersMember_658572f3-673a-46ee-a55e-d1de53237438" xlink:href="mgnx-20250930.xsd#mgnx_SagardHealthcarePartnersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_e42a40d8-c754-4256-9ff8-bbde24390791" xlink:to="loc_mgnx_SagardHealthcarePartnersMember_658572f3-673a-46ee-a55e-d1de53237438" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_2c262f1d-4acd-47b6-a0a3-ba0ec7649059" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyTable_bc0b79c0-d22a-438c-9dcc-f560d84c6d65" xlink:to="loc_us-gaap_TypeOfArrangementAxis_2c262f1d-4acd-47b6-a0a3-ba0ec7649059" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_2c262f1d-4acd-47b6-a0a3-ba0ec7649059_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_2c262f1d-4acd-47b6-a0a3-ba0ec7649059" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_2c262f1d-4acd-47b6-a0a3-ba0ec7649059_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_a1a5d503-282c-41dc-9aa6-82db6e1de8d6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_2c262f1d-4acd-47b6-a0a3-ba0ec7649059" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_a1a5d503-282c-41dc-9aa6-82db6e1de8d6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RoyaltyMonetizationArrangementMember_37b56790-01d9-448d-91de-8004fa6a0512" xlink:href="mgnx-20250930.xsd#mgnx_RoyaltyMonetizationArrangementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_a1a5d503-282c-41dc-9aa6-82db6e1de8d6" xlink:to="loc_mgnx_RoyaltyMonetizationArrangementMember_37b56790-01d9-448d-91de-8004fa6a0512" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProceedsFromSaleOfFutureRoyalties_e89dafff-b347-4cce-b8bf-14ddef3e76de" xlink:href="mgnx-20250930.xsd#mgnx_ProceedsFromSaleOfFutureRoyalties"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_41b28c44-1a88-4f52-b2cd-58c21d18711a" xlink:to="loc_mgnx_ProceedsFromSaleOfFutureRoyalties_e89dafff-b347-4cce-b8bf-14ddef3e76de" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RoyaltyMonetizationArrangementRoyaltyPaymentThreshold_265a133d-4be6-4128-a2bd-ed9e6bbfa8ad" xlink:href="mgnx-20250930.xsd#mgnx_RoyaltyMonetizationArrangementRoyaltyPaymentThreshold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_41b28c44-1a88-4f52-b2cd-58c21d18711a" xlink:to="loc_mgnx_RoyaltyMonetizationArrangementRoyaltyPaymentThreshold_265a133d-4be6-4128-a2bd-ed9e6bbfa8ad" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DeferredTransactionCosts_16899387-173c-4b12-8a55-46e9c68e7dbd" xlink:href="mgnx-20250930.xsd#mgnx_DeferredTransactionCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_41b28c44-1a88-4f52-b2cd-58c21d18711a" xlink:to="loc_mgnx_DeferredTransactionCosts_16899387-173c-4b12-8a55-46e9c68e7dbd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NetProceedsFromSaleOfFutureRoyalties_aa4d9728-66d7-4047-9e57-162d6bee7abc" xlink:href="mgnx-20250930.xsd#mgnx_NetProceedsFromSaleOfFutureRoyalties"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_41b28c44-1a88-4f52-b2cd-58c21d18711a" xlink:to="loc_mgnx_NetProceedsFromSaleOfFutureRoyalties_aa4d9728-66d7-4047-9e57-162d6bee7abc" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RoyaltyMonetizationArrangementInterestRateEffectivePercentage_8d54982c-c655-49a6-8ca0-e92feec98bcc" xlink:href="mgnx-20250930.xsd#mgnx_RoyaltyMonetizationArrangementInterestRateEffectivePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_41b28c44-1a88-4f52-b2cd-58c21d18711a" xlink:to="loc_mgnx_RoyaltyMonetizationArrangementInterestRateEffectivePercentage_8d54982c-c655-49a6-8ca0-e92feec98bcc" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_cedd252d-b4d8-488d-bcfd-57668c8ba1cc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_41b28c44-1a88-4f52-b2cd-58c21d18711a" xlink:to="loc_us-gaap_InterestExpenseNonoperating_cedd252d-b4d8-488d-bcfd-57668c8ba1cc" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RoyaltyMonetizationArrangementRollforwardDetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#RoyaltyMonetizationArrangementRollforwardDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RoyaltyMonetizationArrangementRollforwardDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_3991b06a-2913-4991-bb58-f4a84c025487" xlink:href="mgnx-20250930.xsd#mgnx_LiabilityRelatedToFutureRoyaltyLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_LiabilityRelatedToFutureRoyaltyTable_3608ef65-fee4-4a3f-90d1-5d6e5970fc57" xlink:href="mgnx-20250930.xsd#mgnx_LiabilityRelatedToFutureRoyaltyTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_3991b06a-2913-4991-bb58-f4a84c025487" xlink:to="loc_mgnx_LiabilityRelatedToFutureRoyaltyTable_3608ef65-fee4-4a3f-90d1-5d6e5970fc57" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_7457bf82-415d-4f4b-9515-d67b29d97219" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyTable_3608ef65-fee4-4a3f-90d1-5d6e5970fc57" xlink:to="loc_srt_CounterpartyNameAxis_7457bf82-415d-4f4b-9515-d67b29d97219" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_7457bf82-415d-4f4b-9515-d67b29d97219_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_7457bf82-415d-4f4b-9515-d67b29d97219" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_7457bf82-415d-4f4b-9515-d67b29d97219_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d34ecbe3-8508-41b7-8cc7-70d9d3ea4995" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_7457bf82-415d-4f4b-9515-d67b29d97219" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d34ecbe3-8508-41b7-8cc7-70d9d3ea4995" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_SagardHealthcarePartnersMember_eb6c9cca-3d79-444f-9c21-228a5418d65d" xlink:href="mgnx-20250930.xsd#mgnx_SagardHealthcarePartnersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d34ecbe3-8508-41b7-8cc7-70d9d3ea4995" xlink:to="loc_mgnx_SagardHealthcarePartnersMember_eb6c9cca-3d79-444f-9c21-228a5418d65d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_a0932cc3-f0ce-4db3-99be-d65b10a238fa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyTable_3608ef65-fee4-4a3f-90d1-5d6e5970fc57" xlink:to="loc_us-gaap_TypeOfArrangementAxis_a0932cc3-f0ce-4db3-99be-d65b10a238fa" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_a0932cc3-f0ce-4db3-99be-d65b10a238fa_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_a0932cc3-f0ce-4db3-99be-d65b10a238fa" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_a0932cc3-f0ce-4db3-99be-d65b10a238fa_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_9d2256e9-f748-4f28-89c5-0e7427ba7d2e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_a0932cc3-f0ce-4db3-99be-d65b10a238fa" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_9d2256e9-f748-4f28-89c5-0e7427ba7d2e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RoyaltyMonetizationArrangementMember_946edff6-a63b-4cf3-ad41-a6e4bb317ea6" xlink:href="mgnx-20250930.xsd#mgnx_RoyaltyMonetizationArrangementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_9d2256e9-f748-4f28-89c5-0e7427ba7d2e" xlink:to="loc_mgnx_RoyaltyMonetizationArrangementMember_946edff6-a63b-4cf3-ad41-a6e4bb317ea6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_LiabilityRelatedToFutureRoyaltiesRollForward_075d5088-b725-4822-a5bf-facee9279e4b" xlink:href="mgnx-20250930.xsd#mgnx_LiabilityRelatedToFutureRoyaltiesRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_3991b06a-2913-4991-bb58-f4a84c025487" xlink:to="loc_mgnx_LiabilityRelatedToFutureRoyaltiesRollForward_075d5088-b725-4822-a5bf-facee9279e4b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_LiabilityRelatedToFutureRoyalties_3816d126-982a-4d6c-a74f-c5e0cf2a121e" xlink:href="mgnx-20250930.xsd#mgnx_LiabilityRelatedToFutureRoyalties"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltiesRollForward_075d5088-b725-4822-a5bf-facee9279e4b" xlink:to="loc_mgnx_LiabilityRelatedToFutureRoyalties_3816d126-982a-4d6c-a74f-c5e0cf2a121e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProceedsFromSaleOfFutureRoyalties_ed36d818-c068-40ce-9ff5-a260b926842a" xlink:href="mgnx-20250930.xsd#mgnx_ProceedsFromSaleOfFutureRoyalties"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltiesRollForward_075d5088-b725-4822-a5bf-facee9279e4b" xlink:to="loc_mgnx_ProceedsFromSaleOfFutureRoyalties_ed36d818-c068-40ce-9ff5-a260b926842a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DeferredTransactionCosts_9f69949a-a10b-4218-a2ee-c817dded734f" xlink:href="mgnx-20250930.xsd#mgnx_DeferredTransactionCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltiesRollForward_075d5088-b725-4822-a5bf-facee9279e4b" xlink:to="loc_mgnx_DeferredTransactionCosts_9f69949a-a10b-4218-a2ee-c817dded734f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NoncashRoyaltyRevenuePayable_ad3254e9-e40e-4af2-abae-4a447c714540" xlink:href="mgnx-20250930.xsd#mgnx_NoncashRoyaltyRevenuePayable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltiesRollForward_075d5088-b725-4822-a5bf-facee9279e4b" xlink:to="loc_mgnx_NoncashRoyaltyRevenuePayable_ad3254e9-e40e-4af2-abae-4a447c714540" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_dc05ede1-dc38-45f4-82ce-2dedd19b6179" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltiesRollForward_075d5088-b725-4822-a5bf-facee9279e4b" xlink:to="loc_us-gaap_InterestExpenseNonoperating_dc05ede1-dc38-45f4-82ce-2dedd19b6179" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_LiabilityRelatedToFutureRoyalties_cba805fc-d3a5-4b19-92a8-ba22317f19c2" xlink:href="mgnx-20250930.xsd#mgnx_LiabilityRelatedToFutureRoyalties"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/StockholdersEquityDetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#StockholdersEquityDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/StockholdersEquityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_07441f95-a47b-498c-bd0c-98a596d0f107" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_5faf6bdf-3573-4f40-9246-e6b50bebfe73" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_07441f95-a47b-498c-bd0c-98a596d0f107" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_5faf6bdf-3573-4f40-9246-e6b50bebfe73" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_fbafb58b-2570-497c-930f-55ab08180f4f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_5faf6bdf-3573-4f40-9246-e6b50bebfe73" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_fbafb58b-2570-497c-930f-55ab08180f4f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_fbafb58b-2570-497c-930f-55ab08180f4f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_fbafb58b-2570-497c-930f-55ab08180f4f" xlink:to="loc_us-gaap_EquityComponentDomain_fbafb58b-2570-497c-930f-55ab08180f4f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_11b1faad-7923-4bb6-95bb-85c1f33a1858" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_fbafb58b-2570-497c-930f-55ab08180f4f" xlink:to="loc_us-gaap_EquityComponentDomain_11b1faad-7923-4bb6-95bb-85c1f33a1858" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_8d4a666f-8a25-4095-9d53-f5a0c66e6411" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_11b1faad-7923-4bb6-95bb-85c1f33a1858" xlink:to="loc_us-gaap_CommonStockMember_8d4a666f-8a25-4095-9d53-f5a0c66e6411" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_1f8afe55-d8c2-4fe8-bdac-41a87c1ce5f9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_5faf6bdf-3573-4f40-9246-e6b50bebfe73" xlink:to="loc_us-gaap_PlanNameAxis_1f8afe55-d8c2-4fe8-bdac-41a87c1ce5f9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_1f8afe55-d8c2-4fe8-bdac-41a87c1ce5f9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_1f8afe55-d8c2-4fe8-bdac-41a87c1ce5f9" xlink:to="loc_us-gaap_PlanNameDomain_1f8afe55-d8c2-4fe8-bdac-41a87c1ce5f9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_64f035de-08be-4519-968e-038a50c726c5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_1f8afe55-d8c2-4fe8-bdac-41a87c1ce5f9" xlink:to="loc_us-gaap_PlanNameDomain_64f035de-08be-4519-968e-038a50c726c5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_StockIncentivePlan2023MemberMember_39954573-6988-42aa-a6b5-8799f311ac09" xlink:href="mgnx-20250930.xsd#mgnx_StockIncentivePlan2023MemberMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_64f035de-08be-4519-968e-038a50c726c5" xlink:to="loc_mgnx_StockIncentivePlan2023MemberMember_39954573-6988-42aa-a6b5-8799f311ac09" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_06562cae-be5e-41b6-8202-15ffb9e2e95f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_07441f95-a47b-498c-bd0c-98a596d0f107" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_06562cae-be5e-41b6-8202-15ffb9e2e95f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_cedba575-ed80-42b8-a934-aff21813d1a1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_07441f95-a47b-498c-bd0c-98a596d0f107" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_cedba575-ed80-42b8-a934-aff21813d1a1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromStockOptionsExercised_a832f6fc-7d24-4919-af8e-11f6430d459c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProceedsFromStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_07441f95-a47b-498c-bd0c-98a596d0f107" xlink:to="loc_us-gaap_ProceedsFromStockOptionsExercised_a832f6fc-7d24-4919-af8e-11f6430d459c" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RevenueIncyteCorporationDetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#RevenueIncyteCorporationDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RevenueIncyteCorporationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1827a5a5-ce23-4d82-99c3-e7a904e4ed52" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1827a5a5-ce23-4d82-99c3-e7a904e4ed52" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_a7b20c9e-c434-47c7-8558-36a337d5bae0" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1827a5a5-ce23-4d82-99c3-e7a904e4ed52" xlink:to="loc_srt_ProductOrServiceAxis_a7b20c9e-c434-47c7-8558-36a337d5bae0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_a7b20c9e-c434-47c7-8558-36a337d5bae0_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_a7b20c9e-c434-47c7-8558-36a337d5bae0" xlink:to="loc_srt_ProductsAndServicesDomain_a7b20c9e-c434-47c7-8558-36a337d5bae0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_92816592-efa5-4800-bd90-7bf800e402b1" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_a7b20c9e-c434-47c7-8558-36a337d5bae0" xlink:to="loc_srt_ProductsAndServicesDomain_92816592-efa5-4800-bd90-7bf800e402b1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromLicenseAgreementsMember_31810ad5-15a4-49aa-9650-4e1c469e37cc" xlink:href="mgnx-20250930.xsd#mgnx_RevenuesFromLicenseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_92816592-efa5-4800-bd90-7bf800e402b1" xlink:to="loc_mgnx_RevenuesFromLicenseAgreementsMember_31810ad5-15a4-49aa-9650-4e1c469e37cc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromCMOAgreementsMemberMember_5c7c952e-5c28-45a7-b44d-821d908867d7" xlink:href="mgnx-20250930.xsd#mgnx_RevenuesFromCMOAgreementsMemberMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_92816592-efa5-4800-bd90-7bf800e402b1" xlink:to="loc_mgnx_RevenuesFromCMOAgreementsMemberMember_5c7c952e-5c28-45a7-b44d-821d908867d7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromCMOAmendmentAgreementMember_6fe73de3-944b-4f18-9334-352c14b34006" xlink:href="mgnx-20250930.xsd#mgnx_RevenuesFromCMOAmendmentAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_92816592-efa5-4800-bd90-7bf800e402b1" xlink:to="loc_mgnx_RevenuesFromCMOAmendmentAgreementMember_6fe73de3-944b-4f18-9334-352c14b34006" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ManufacturingServicesMember_8820542d-cad6-4795-a775-21e05f051e89" xlink:href="mgnx-20250930.xsd#mgnx_ManufacturingServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_92816592-efa5-4800-bd90-7bf800e402b1" xlink:to="loc_mgnx_ManufacturingServicesMember_8820542d-cad6-4795-a775-21e05f051e89" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_7aab9b3e-1b81-4e18-9a91-6fc595637541" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1827a5a5-ce23-4d82-99c3-e7a904e4ed52" xlink:to="loc_srt_RangeAxis_7aab9b3e-1b81-4e18-9a91-6fc595637541" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_7aab9b3e-1b81-4e18-9a91-6fc595637541_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_7aab9b3e-1b81-4e18-9a91-6fc595637541" xlink:to="loc_srt_RangeMember_7aab9b3e-1b81-4e18-9a91-6fc595637541_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_0dfab44b-cef4-4b06-8da6-c89a50bdea54" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_7aab9b3e-1b81-4e18-9a91-6fc595637541" xlink:to="loc_srt_RangeMember_0dfab44b-cef4-4b06-8da6-c89a50bdea54" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_81110521-2f19-4ae8-9626-ec60eab9f029" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_0dfab44b-cef4-4b06-8da6-c89a50bdea54" xlink:to="loc_srt_MinimumMember_81110521-2f19-4ae8-9626-ec60eab9f029" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_375ac61e-7f75-4cb6-8903-47a8689fe5be" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_0dfab44b-cef4-4b06-8da6-c89a50bdea54" xlink:to="loc_srt_MaximumMember_375ac61e-7f75-4cb6-8903-47a8689fe5be" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_3935e913-4e55-4b60-9314-8966d4bf6c25" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1827a5a5-ce23-4d82-99c3-e7a904e4ed52" xlink:to="loc_srt_CounterpartyNameAxis_3935e913-4e55-4b60-9314-8966d4bf6c25" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_3935e913-4e55-4b60-9314-8966d4bf6c25_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_3935e913-4e55-4b60-9314-8966d4bf6c25" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_3935e913-4e55-4b60-9314-8966d4bf6c25_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_cc986339-a690-45c0-88d8-506d5bb01eba" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_3935e913-4e55-4b60-9314-8966d4bf6c25" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_cc986339-a690-45c0-88d8-506d5bb01eba" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteCorporationMember_ef75b4fe-aee6-4123-b121-67f3b7612cfe" xlink:href="mgnx-20250930.xsd#mgnx_IncyteCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_cc986339-a690-45c0-88d8-506d5bb01eba" xlink:to="loc_mgnx_IncyteCorporationMember_ef75b4fe-aee6-4123-b121-67f3b7612cfe" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_GileadMember_28fffad3-1161-495c-8007-aabd34f5512d" xlink:href="mgnx-20250930.xsd#mgnx_GileadMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_cc986339-a690-45c0-88d8-506d5bb01eba" xlink:to="loc_mgnx_GileadMember_28fffad3-1161-495c-8007-aabd34f5512d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_15620152-fc79-4f78-b1f3-c2342ba477e4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1827a5a5-ce23-4d82-99c3-e7a904e4ed52" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_15620152-fc79-4f78-b1f3-c2342ba477e4" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_15620152-fc79-4f78-b1f3-c2342ba477e4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_15620152-fc79-4f78-b1f3-c2342ba477e4" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_15620152-fc79-4f78-b1f3-c2342ba477e4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_3779883f-769a-4ec8-bf14-aba309a6f2bd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_15620152-fc79-4f78-b1f3-c2342ba477e4" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_3779883f-769a-4ec8-bf14-aba309a6f2bd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteMGA012AgreementMember_7856ec94-57e1-462a-b654-d79d94fbe1b8" xlink:href="mgnx-20250930.xsd#mgnx_IncyteMGA012AgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_3779883f-769a-4ec8-bf14-aba309a6f2bd" xlink:to="loc_mgnx_IncyteMGA012AgreementMember_7856ec94-57e1-462a-b654-d79d94fbe1b8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteCommercialSupplyAgreementMember_1aac9d36-32dc-4769-8188-c3f9c537dc4c" xlink:href="mgnx-20250930.xsd#mgnx_IncyteCommercialSupplyAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_3779883f-769a-4ec8-bf14-aba309a6f2bd" xlink:to="loc_mgnx_IncyteCommercialSupplyAgreementMember_1aac9d36-32dc-4769-8188-c3f9c537dc4c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_GileadFirstResearchProgramMember_1be394bc-076f-4762-a321-2dd32148878c" xlink:href="mgnx-20250930.xsd#mgnx_GileadFirstResearchProgramMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_3779883f-769a-4ec8-bf14-aba309a6f2bd" xlink:to="loc_mgnx_GileadFirstResearchProgramMember_1be394bc-076f-4762-a321-2dd32148878c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis_7ab5e6c3-0f0b-4837-bcff-b39899628649" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1827a5a5-ce23-4d82-99c3-e7a904e4ed52" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis_7ab5e6c3-0f0b-4837-bcff-b39899628649" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_16eb9b24-08d8-4dc3-9822-881b5252f0cd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_16eb9b24-08d8-4dc3-9822-881b5252f0cd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_abec8822-9fea-45c9-9767-b73c583beb51" xlink:href="mgnx-20250930.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_NonRefundableUpfrontFees_abec8822-9fea-45c9-9767-b73c583beb51" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_TotalAnnualFixedPayments_0dbfda17-b812-4c39-b2bb-8998977996eb" xlink:href="mgnx-20250930.xsd#mgnx_TotalAnnualFixedPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_TotalAnnualFixedPayments_0dbfda17-b812-4c39-b2bb-8998977996eb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_AdditionalAnnualFixedPayments_567ad927-c1e9-4642-89f8-2c2a3e2c45f1" xlink:href="mgnx-20250930.xsd#mgnx_AdditionalAnnualFixedPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_AdditionalAnnualFixedPayments_567ad927-c1e9-4642-89f8-2c2a3e2c45f1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuePerformanceObligationExtensionTerm_78708a26-2b4d-4975-8b2c-b792e6207933" xlink:href="mgnx-20250930.xsd#mgnx_RevenuePerformanceObligationExtensionTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_RevenuePerformanceObligationExtensionTerm_78708a26-2b4d-4975-8b2c-b792e6207933" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_44816ff7-24a5-44d5-87b3-6f232f992e74" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_Revenues_44816ff7-24a5-44d5-87b3-6f232f992e74" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_2163c291-7df0-43b3-8167-2f6e1795581c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_ContractWithCustomerLiability_2163c291-7df0-43b3-8167-2f6e1795581c" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_02d61b92-287c-46a4-9970-fb82f5fe3de8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_02d61b92-287c-46a4-9970-fb82f5fe3de8" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_67324d33-0c45-4665-a914-dcfd462ca4bf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_67324d33-0c45-4665-a914-dcfd462ca4bf" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_68aa4f67-f827-4284-9d64-6bc0f5643b5b" xlink:href="mgnx-20250930.xsd#mgnx_PotentialCommercialMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_68aa4f67-f827-4284-9d64-6bc0f5643b5b" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_bcd04572-6f74-4c0a-99d3-058b5453eed7" xlink:href="mgnx-20250930.xsd#mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_bcd04572-6f74-4c0a-99d3-058b5453eed7" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_95bae9af-0434-4c5b-a8ee-7ec624cc02d4" xlink:href="mgnx-20250930.xsd#mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_95bae9af-0434-4c5b-a8ee-7ec624cc02d4" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProceedsfromRoyaltiesPercent_be164164-5063-4a71-85a0-627b3a0d276f" xlink:href="mgnx-20250930.xsd#mgnx_ProceedsfromRoyaltiesPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_ProceedsfromRoyaltiesPercent_be164164-5063-4a71-85a0-627b3a0d276f" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementTransactionPrice_6c86142c-918d-4ea8-bc1b-052117487955" xlink:href="mgnx-20250930.xsd#mgnx_CollaborativeAgreementTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_CollaborativeAgreementTransactionPrice_6c86142c-918d-4ea8-bc1b-052117487955" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_fce8507f-6eff-43a7-a9da-f07eca39aaa5" xlink:href="mgnx-20250930.xsd#mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_fce8507f-6eff-43a7-a9da-f07eca39aaa5" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NumberOfPerformanceObligations_bacf4b04-d290-4cf3-943f-6b6f91f3fa3f" xlink:href="mgnx-20250930.xsd#mgnx_NumberOfPerformanceObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_NumberOfPerformanceObligations_bacf4b04-d290-4cf3-943f-6b6f91f3fa3f" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligation_8cf2bac1-0ce9-4167-8b0b-9d0aa1a971c7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligation_8cf2bac1-0ce9-4167-8b0b-9d0aa1a971c7" xlink:type="arc" order="16"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RevenueIncyteCorporationDetails_1" xlink:type="simple" xlink:href="mgnx-20250930.xsd#RevenueIncyteCorporationDetails_1"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RevenueIncyteCorporationDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1827a5a5-ce23-4d82-99c3-e7a904e4ed52" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1827a5a5-ce23-4d82-99c3-e7a904e4ed52" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_a7b20c9e-c434-47c7-8558-36a337d5bae0" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1827a5a5-ce23-4d82-99c3-e7a904e4ed52" xlink:to="loc_srt_ProductOrServiceAxis_a7b20c9e-c434-47c7-8558-36a337d5bae0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_a7b20c9e-c434-47c7-8558-36a337d5bae0_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_a7b20c9e-c434-47c7-8558-36a337d5bae0" xlink:to="loc_srt_ProductsAndServicesDomain_a7b20c9e-c434-47c7-8558-36a337d5bae0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_92816592-efa5-4800-bd90-7bf800e402b1" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_a7b20c9e-c434-47c7-8558-36a337d5bae0" xlink:to="loc_srt_ProductsAndServicesDomain_92816592-efa5-4800-bd90-7bf800e402b1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromLicenseAgreementsMember_31810ad5-15a4-49aa-9650-4e1c469e37cc" xlink:href="mgnx-20250930.xsd#mgnx_RevenuesFromLicenseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_92816592-efa5-4800-bd90-7bf800e402b1" xlink:to="loc_mgnx_RevenuesFromLicenseAgreementsMember_31810ad5-15a4-49aa-9650-4e1c469e37cc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromCMOAgreementsMemberMember_5c7c952e-5c28-45a7-b44d-821d908867d7" xlink:href="mgnx-20250930.xsd#mgnx_RevenuesFromCMOAgreementsMemberMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_92816592-efa5-4800-bd90-7bf800e402b1" xlink:to="loc_mgnx_RevenuesFromCMOAgreementsMemberMember_5c7c952e-5c28-45a7-b44d-821d908867d7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromCMOAmendmentAgreementMember_6fe73de3-944b-4f18-9334-352c14b34006" xlink:href="mgnx-20250930.xsd#mgnx_RevenuesFromCMOAmendmentAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_92816592-efa5-4800-bd90-7bf800e402b1" xlink:to="loc_mgnx_RevenuesFromCMOAmendmentAgreementMember_6fe73de3-944b-4f18-9334-352c14b34006" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ManufacturingServicesMember_8820542d-cad6-4795-a775-21e05f051e89" xlink:href="mgnx-20250930.xsd#mgnx_ManufacturingServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_92816592-efa5-4800-bd90-7bf800e402b1" xlink:to="loc_mgnx_ManufacturingServicesMember_8820542d-cad6-4795-a775-21e05f051e89" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_7aab9b3e-1b81-4e18-9a91-6fc595637541" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1827a5a5-ce23-4d82-99c3-e7a904e4ed52" xlink:to="loc_srt_RangeAxis_7aab9b3e-1b81-4e18-9a91-6fc595637541" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_7aab9b3e-1b81-4e18-9a91-6fc595637541_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_7aab9b3e-1b81-4e18-9a91-6fc595637541" xlink:to="loc_srt_RangeMember_7aab9b3e-1b81-4e18-9a91-6fc595637541_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_0dfab44b-cef4-4b06-8da6-c89a50bdea54" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_7aab9b3e-1b81-4e18-9a91-6fc595637541" xlink:to="loc_srt_RangeMember_0dfab44b-cef4-4b06-8da6-c89a50bdea54" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_81110521-2f19-4ae8-9626-ec60eab9f029" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_0dfab44b-cef4-4b06-8da6-c89a50bdea54" xlink:to="loc_srt_MinimumMember_81110521-2f19-4ae8-9626-ec60eab9f029" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_375ac61e-7f75-4cb6-8903-47a8689fe5be" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_0dfab44b-cef4-4b06-8da6-c89a50bdea54" xlink:to="loc_srt_MaximumMember_375ac61e-7f75-4cb6-8903-47a8689fe5be" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_3935e913-4e55-4b60-9314-8966d4bf6c25" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1827a5a5-ce23-4d82-99c3-e7a904e4ed52" xlink:to="loc_srt_CounterpartyNameAxis_3935e913-4e55-4b60-9314-8966d4bf6c25" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_3935e913-4e55-4b60-9314-8966d4bf6c25_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_3935e913-4e55-4b60-9314-8966d4bf6c25" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_3935e913-4e55-4b60-9314-8966d4bf6c25_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_cc986339-a690-45c0-88d8-506d5bb01eba" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_3935e913-4e55-4b60-9314-8966d4bf6c25" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_cc986339-a690-45c0-88d8-506d5bb01eba" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteCorporationMember_ef75b4fe-aee6-4123-b121-67f3b7612cfe" xlink:href="mgnx-20250930.xsd#mgnx_IncyteCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_cc986339-a690-45c0-88d8-506d5bb01eba" xlink:to="loc_mgnx_IncyteCorporationMember_ef75b4fe-aee6-4123-b121-67f3b7612cfe" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_GileadMember_28fffad3-1161-495c-8007-aabd34f5512d" xlink:href="mgnx-20250930.xsd#mgnx_GileadMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_cc986339-a690-45c0-88d8-506d5bb01eba" xlink:to="loc_mgnx_GileadMember_28fffad3-1161-495c-8007-aabd34f5512d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_15620152-fc79-4f78-b1f3-c2342ba477e4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1827a5a5-ce23-4d82-99c3-e7a904e4ed52" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_15620152-fc79-4f78-b1f3-c2342ba477e4" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_15620152-fc79-4f78-b1f3-c2342ba477e4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_15620152-fc79-4f78-b1f3-c2342ba477e4" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_15620152-fc79-4f78-b1f3-c2342ba477e4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_3779883f-769a-4ec8-bf14-aba309a6f2bd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_15620152-fc79-4f78-b1f3-c2342ba477e4" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_3779883f-769a-4ec8-bf14-aba309a6f2bd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteMGA012AgreementMember_7856ec94-57e1-462a-b654-d79d94fbe1b8" xlink:href="mgnx-20250930.xsd#mgnx_IncyteMGA012AgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_3779883f-769a-4ec8-bf14-aba309a6f2bd" xlink:to="loc_mgnx_IncyteMGA012AgreementMember_7856ec94-57e1-462a-b654-d79d94fbe1b8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteCommercialSupplyAgreementMember_1aac9d36-32dc-4769-8188-c3f9c537dc4c" xlink:href="mgnx-20250930.xsd#mgnx_IncyteCommercialSupplyAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_3779883f-769a-4ec8-bf14-aba309a6f2bd" xlink:to="loc_mgnx_IncyteCommercialSupplyAgreementMember_1aac9d36-32dc-4769-8188-c3f9c537dc4c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_GileadFirstResearchProgramMember_1be394bc-076f-4762-a321-2dd32148878c" xlink:href="mgnx-20250930.xsd#mgnx_GileadFirstResearchProgramMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_3779883f-769a-4ec8-bf14-aba309a6f2bd" xlink:to="loc_mgnx_GileadFirstResearchProgramMember_1be394bc-076f-4762-a321-2dd32148878c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_16eb9b24-08d8-4dc3-9822-881b5252f0cd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_16eb9b24-08d8-4dc3-9822-881b5252f0cd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_abec8822-9fea-45c9-9767-b73c583beb51" xlink:href="mgnx-20250930.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_NonRefundableUpfrontFees_abec8822-9fea-45c9-9767-b73c583beb51" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_TotalAnnualFixedPayments_0dbfda17-b812-4c39-b2bb-8998977996eb" xlink:href="mgnx-20250930.xsd#mgnx_TotalAnnualFixedPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_TotalAnnualFixedPayments_0dbfda17-b812-4c39-b2bb-8998977996eb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_AdditionalAnnualFixedPayments_567ad927-c1e9-4642-89f8-2c2a3e2c45f1" xlink:href="mgnx-20250930.xsd#mgnx_AdditionalAnnualFixedPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_AdditionalAnnualFixedPayments_567ad927-c1e9-4642-89f8-2c2a3e2c45f1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuePerformanceObligationExtensionTerm_78708a26-2b4d-4975-8b2c-b792e6207933" xlink:href="mgnx-20250930.xsd#mgnx_RevenuePerformanceObligationExtensionTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_RevenuePerformanceObligationExtensionTerm_78708a26-2b4d-4975-8b2c-b792e6207933" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_44816ff7-24a5-44d5-87b3-6f232f992e74" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_Revenues_44816ff7-24a5-44d5-87b3-6f232f992e74" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_2163c291-7df0-43b3-8167-2f6e1795581c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_ContractWithCustomerLiability_2163c291-7df0-43b3-8167-2f6e1795581c" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_02d61b92-287c-46a4-9970-fb82f5fe3de8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_02d61b92-287c-46a4-9970-fb82f5fe3de8" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_67324d33-0c45-4665-a914-dcfd462ca4bf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_67324d33-0c45-4665-a914-dcfd462ca4bf" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_68aa4f67-f827-4284-9d64-6bc0f5643b5b" xlink:href="mgnx-20250930.xsd#mgnx_PotentialCommercialMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_68aa4f67-f827-4284-9d64-6bc0f5643b5b" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_bcd04572-6f74-4c0a-99d3-058b5453eed7" xlink:href="mgnx-20250930.xsd#mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_bcd04572-6f74-4c0a-99d3-058b5453eed7" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_95bae9af-0434-4c5b-a8ee-7ec624cc02d4" xlink:href="mgnx-20250930.xsd#mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_95bae9af-0434-4c5b-a8ee-7ec624cc02d4" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProceedsfromRoyaltiesPercent_be164164-5063-4a71-85a0-627b3a0d276f" xlink:href="mgnx-20250930.xsd#mgnx_ProceedsfromRoyaltiesPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_ProceedsfromRoyaltiesPercent_be164164-5063-4a71-85a0-627b3a0d276f" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementTransactionPrice_6c86142c-918d-4ea8-bc1b-052117487955" xlink:href="mgnx-20250930.xsd#mgnx_CollaborativeAgreementTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_CollaborativeAgreementTransactionPrice_6c86142c-918d-4ea8-bc1b-052117487955" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_fce8507f-6eff-43a7-a9da-f07eca39aaa5" xlink:href="mgnx-20250930.xsd#mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_fce8507f-6eff-43a7-a9da-f07eca39aaa5" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NumberOfPerformanceObligations_bacf4b04-d290-4cf3-943f-6b6f91f3fa3f" xlink:href="mgnx-20250930.xsd#mgnx_NumberOfPerformanceObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_mgnx_NumberOfPerformanceObligations_bacf4b04-d290-4cf3-943f-6b6f91f3fa3f" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligation_8cf2bac1-0ce9-4167-8b0b-9d0aa1a971c7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_fd296075-1af2-43bf-9bd5-0383a21d624c" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligation_8cf2bac1-0ce9-4167-8b0b-9d0aa1a971c7" xlink:type="arc" order="16"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RevenueGileadScienceIncDetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#RevenueGileadScienceIncDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RevenueGileadScienceIncDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_729ae64c-4442-44e9-870e-21c3c565092d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_38d8f27e-eb1d-4ca1-a255-8934763b7ba7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_729ae64c-4442-44e9-870e-21c3c565092d" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_38d8f27e-eb1d-4ca1-a255-8934763b7ba7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_f6530d69-83a4-4bc8-b806-4e1dafad9e08" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_38d8f27e-eb1d-4ca1-a255-8934763b7ba7" xlink:to="loc_srt_CounterpartyNameAxis_f6530d69-83a4-4bc8-b806-4e1dafad9e08" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f6530d69-83a4-4bc8-b806-4e1dafad9e08_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_f6530d69-83a4-4bc8-b806-4e1dafad9e08" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f6530d69-83a4-4bc8-b806-4e1dafad9e08_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_e3552389-2d2e-4cf5-86fe-d9f2193093c2" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_f6530d69-83a4-4bc8-b806-4e1dafad9e08" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_e3552389-2d2e-4cf5-86fe-d9f2193093c2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_GileadMember_c43a6def-5b0d-4b6d-8640-130d248a8976" xlink:href="mgnx-20250930.xsd#mgnx_GileadMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_e3552389-2d2e-4cf5-86fe-d9f2193093c2" xlink:to="loc_mgnx_GileadMember_c43a6def-5b0d-4b6d-8640-130d248a8976" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_83abc645-b9d3-4ca4-89d0-00ff6b7fe608" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_38d8f27e-eb1d-4ca1-a255-8934763b7ba7" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_83abc645-b9d3-4ca4-89d0-00ff6b7fe608" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_83abc645-b9d3-4ca4-89d0-00ff6b7fe608_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_83abc645-b9d3-4ca4-89d0-00ff6b7fe608" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_83abc645-b9d3-4ca4-89d0-00ff6b7fe608_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_0e9eb095-ae07-4e79-8e94-602f6588ac6e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_83abc645-b9d3-4ca4-89d0-00ff6b7fe608" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_0e9eb095-ae07-4e79-8e94-602f6588ac6e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_A2022GileadCollaborationAndLicenseAgreementMember_0f27f362-062a-441c-9fc8-08ce12f5ef30" xlink:href="mgnx-20250930.xsd#mgnx_A2022GileadCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_0e9eb095-ae07-4e79-8e94-602f6588ac6e" xlink:to="loc_mgnx_A2022GileadCollaborationAndLicenseAgreementMember_0f27f362-062a-441c-9fc8-08ce12f5ef30" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_GileadFirstResearchProgramMember_b04289c7-f9f7-4b3f-91f4-49c8eb243177" xlink:href="mgnx-20250930.xsd#mgnx_GileadFirstResearchProgramMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_0e9eb095-ae07-4e79-8e94-602f6588ac6e" xlink:to="loc_mgnx_GileadFirstResearchProgramMember_b04289c7-f9f7-4b3f-91f4-49c8eb243177" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_e2b86bd3-6360-463e-af77-9c59c4d8dab6" xlink:href="mgnx-20250930.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_729ae64c-4442-44e9-870e-21c3c565092d" xlink:to="loc_mgnx_NonRefundableUpfrontFees_e2b86bd3-6360-463e-af77-9c59c4d8dab6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_8250d259-1e77-4f0b-b2a1-4155a7f712d3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_729ae64c-4442-44e9-870e-21c3c565092d" xlink:to="loc_us-gaap_Revenues_8250d259-1e77-4f0b-b2a1-4155a7f712d3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_45bd888f-836f-40da-8092-59a217b68ccd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_729ae64c-4442-44e9-870e-21c3c565092d" xlink:to="loc_us-gaap_ContractWithCustomerLiability_45bd888f-836f-40da-8092-59a217b68ccd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_eb9ae325-b088-4c01-92a8-7bad50603f0e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_729ae64c-4442-44e9-870e-21c3c565092d" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_eb9ae325-b088-4c01-92a8-7bad50603f0e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_30a3c68d-945f-4d42-8175-2051d3de06b8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_729ae64c-4442-44e9-870e-21c3c565092d" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_30a3c68d-945f-4d42-8175-2051d3de06b8" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligation_bc67bc1f-22a4-43de-8c00-449eccf197bb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_729ae64c-4442-44e9-870e-21c3c565092d" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligation_bc67bc1f-22a4-43de-8c00-449eccf197bb" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialTargetNominationOptionFeesAndMilestonePayments_7515e311-6588-40e1-b154-5c44603f7224" xlink:href="mgnx-20250930.xsd#mgnx_PotentialTargetNominationOptionFeesAndMilestonePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_729ae64c-4442-44e9-870e-21c3c565092d" xlink:to="loc_mgnx_PotentialTargetNominationOptionFeesAndMilestonePayments_7515e311-6588-40e1-b154-5c44603f7224" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_OptInFee_f47d3cc1-7645-44d3-a7bf-1d3ed7afe8d0" xlink:href="mgnx-20250930.xsd#mgnx_OptInFee"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_729ae64c-4442-44e9-870e-21c3c565092d" xlink:to="loc_mgnx_OptInFee_f47d3cc1-7645-44d3-a7bf-1d3ed7afe8d0" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RevenueProventionDetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#RevenueProventionDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RevenueProventionDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_b8f1b700-6a65-4bc3-b4f7-338e9f0e8d2a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_f8bf999d-ddcf-4bf2-8b26-d9713183b9f0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_b8f1b700-6a65-4bc3-b4f7-338e9f0e8d2a" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_f8bf999d-ddcf-4bf2-8b26-d9713183b9f0" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_2cb6d5d3-6d68-43cb-8918-e43782b92ecd" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_f8bf999d-ddcf-4bf2-8b26-d9713183b9f0" xlink:to="loc_srt_ProductOrServiceAxis_2cb6d5d3-6d68-43cb-8918-e43782b92ecd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_2cb6d5d3-6d68-43cb-8918-e43782b92ecd_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_2cb6d5d3-6d68-43cb-8918-e43782b92ecd" xlink:to="loc_srt_ProductsAndServicesDomain_2cb6d5d3-6d68-43cb-8918-e43782b92ecd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_fb102fb2-189f-48b8-be1a-54b3cbc88135" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_2cb6d5d3-6d68-43cb-8918-e43782b92ecd" xlink:to="loc_srt_ProductsAndServicesDomain_fb102fb2-189f-48b8-be1a-54b3cbc88135" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromLicenseAgreementsMember_ea2a7395-839c-4d05-9ddc-dfab86f8dcfa" xlink:href="mgnx-20250930.xsd#mgnx_RevenuesFromLicenseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_fb102fb2-189f-48b8-be1a-54b3cbc88135" xlink:to="loc_mgnx_RevenuesFromLicenseAgreementsMember_ea2a7395-839c-4d05-9ddc-dfab86f8dcfa" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_bef6802f-c67e-44f3-a24c-75c127f7aabe" xlink:href="mgnx-20250930.xsd#mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_b8f1b700-6a65-4bc3-b4f7-338e9f0e8d2a" xlink:to="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_bef6802f-c67e-44f3-a24c-75c127f7aabe" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_6bfea378-4079-483f-9d9f-2272ce0328e4" xlink:href="mgnx-20250930.xsd#mgnx_PotentialCommercialMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_b8f1b700-6a65-4bc3-b4f7-338e9f0e8d2a" xlink:to="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_6bfea378-4079-483f-9d9f-2272ce0328e4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_75e68d20-2c20-42e8-a6cc-4b74a34877cf" xlink:href="mgnx-20250930.xsd#mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_b8f1b700-6a65-4bc3-b4f7-338e9f0e8d2a" xlink:to="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_75e68d20-2c20-42e8-a6cc-4b74a34877cf" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementTransactionPrice_3cc880f1-6015-44b7-97c0-7040345a529f" xlink:href="mgnx-20250930.xsd#mgnx_CollaborativeAgreementTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_b8f1b700-6a65-4bc3-b4f7-338e9f0e8d2a" xlink:to="loc_mgnx_CollaborativeAgreementTransactionPrice_3cc880f1-6015-44b7-97c0-7040345a529f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_8232024d-88bd-4063-a98e-55882145c6f3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_b8f1b700-6a65-4bc3-b4f7-338e9f0e8d2a" xlink:to="loc_us-gaap_Revenues_8232024d-88bd-4063-a98e-55882145c6f3" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RevenueSanofiSADetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#RevenueSanofiSADetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RevenueSanofiSADetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4220a067-98e5-483e-a94e-7073411e4c08" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_e6ee172c-5e0a-4299-90a4-ce3fc7634abc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4220a067-98e5-483e-a94e-7073411e4c08" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_e6ee172c-5e0a-4299-90a4-ce3fc7634abc" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_d41cebc4-3545-462d-b671-faf4eadbbb40" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_e6ee172c-5e0a-4299-90a4-ce3fc7634abc" xlink:to="loc_srt_CounterpartyNameAxis_d41cebc4-3545-462d-b671-faf4eadbbb40" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d41cebc4-3545-462d-b671-faf4eadbbb40_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_d41cebc4-3545-462d-b671-faf4eadbbb40" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d41cebc4-3545-462d-b671-faf4eadbbb40_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d11ec12b-9002-4446-972c-1e01490e17be" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_d41cebc4-3545-462d-b671-faf4eadbbb40" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d11ec12b-9002-4446-972c-1e01490e17be" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_SanofiS.A.Member_43babf0a-49cd-44f7-b180-843b8b127d02" xlink:href="mgnx-20250930.xsd#mgnx_SanofiS.A.Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d11ec12b-9002-4446-972c-1e01490e17be" xlink:to="loc_mgnx_SanofiS.A.Member_43babf0a-49cd-44f7-b180-843b8b127d02" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_af25b003-cf94-42f8-8783-6a0277bdb88f" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_e6ee172c-5e0a-4299-90a4-ce3fc7634abc" xlink:to="loc_srt_ProductOrServiceAxis_af25b003-cf94-42f8-8783-6a0277bdb88f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_af25b003-cf94-42f8-8783-6a0277bdb88f_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_af25b003-cf94-42f8-8783-6a0277bdb88f" xlink:to="loc_srt_ProductsAndServicesDomain_af25b003-cf94-42f8-8783-6a0277bdb88f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_6afabf5c-d9e9-433a-8dcd-d40a5e48258f" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_af25b003-cf94-42f8-8783-6a0277bdb88f" xlink:to="loc_srt_ProductsAndServicesDomain_6afabf5c-d9e9-433a-8dcd-d40a5e48258f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RoyaltyMember_367bc0ea-9096-4b1b-a1d9-e0040f4d41b2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RoyaltyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_6afabf5c-d9e9-433a-8dcd-d40a5e48258f" xlink:to="loc_us-gaap_RoyaltyMember_367bc0ea-9096-4b1b-a1d9-e0040f4d41b2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_MilestoneTypeAxis_c6de9964-5504-465a-9f18-59d8ef4a8a48" xlink:href="mgnx-20250930.xsd#mgnx_MilestoneTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_e6ee172c-5e0a-4299-90a4-ce3fc7634abc" xlink:to="loc_mgnx_MilestoneTypeAxis_c6de9964-5504-465a-9f18-59d8ef4a8a48" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_MilestoneTypeDomain_c6de9964-5504-465a-9f18-59d8ef4a8a48_default" xlink:href="mgnx-20250930.xsd#mgnx_MilestoneTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_mgnx_MilestoneTypeAxis_c6de9964-5504-465a-9f18-59d8ef4a8a48" xlink:to="loc_mgnx_MilestoneTypeDomain_c6de9964-5504-465a-9f18-59d8ef4a8a48_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_MilestoneTypeDomain_86cc54fc-01aa-4858-8ebf-80de79b23bbe" xlink:href="mgnx-20250930.xsd#mgnx_MilestoneTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_mgnx_MilestoneTypeAxis_c6de9964-5504-465a-9f18-59d8ef4a8a48" xlink:to="loc_mgnx_MilestoneTypeDomain_86cc54fc-01aa-4858-8ebf-80de79b23bbe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RegulatoryAndCommericalMilestonesMember_f8b7bf40-58ba-4948-9584-d95eae44d2a7" xlink:href="mgnx-20250930.xsd#mgnx_RegulatoryAndCommericalMilestonesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_MilestoneTypeDomain_86cc54fc-01aa-4858-8ebf-80de79b23bbe" xlink:to="loc_mgnx_RegulatoryAndCommericalMilestonesMember_f8b7bf40-58ba-4948-9584-d95eae44d2a7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RegulatoryMilestoneMember_07bbe63b-5654-423e-ba38-609d3c55c0f0" xlink:href="mgnx-20250930.xsd#mgnx_RegulatoryMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_RegulatoryAndCommericalMilestonesMember_f8b7bf40-58ba-4948-9584-d95eae44d2a7" xlink:to="loc_mgnx_RegulatoryMilestoneMember_07bbe63b-5654-423e-ba38-609d3c55c0f0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NetSalesMilestoneMember_3095f606-5a3c-4a94-89aa-1268fd08ba22" xlink:href="mgnx-20250930.xsd#mgnx_NetSalesMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_MilestoneTypeDomain_86cc54fc-01aa-4858-8ebf-80de79b23bbe" xlink:to="loc_mgnx_NetSalesMilestoneMember_3095f606-5a3c-4a94-89aa-1268fd08ba22" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_4ceffb48-0612-49cf-b689-61289bf7bcfd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4220a067-98e5-483e-a94e-7073411e4c08" xlink:to="loc_us-gaap_ContractWithCustomerLiability_4ceffb48-0612-49cf-b689-61289bf7bcfd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueRemainingPerformanceObligationVariableConsiderationAmount_4b1d15a9-14a4-4287-bd74-2b0728206b70" xlink:href="mgnx-20250930.xsd#mgnx_RevenueRemainingPerformanceObligationVariableConsiderationAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4220a067-98e5-483e-a94e-7073411e4c08" xlink:to="loc_mgnx_RevenueRemainingPerformanceObligationVariableConsiderationAmount_4b1d15a9-14a4-4287-bd74-2b0728206b70" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueRemainingPerformanceObligationVariableConsiderationRoyaltyPercentage_ecbb214f-4dc6-4124-819a-2feca7117bec" xlink:href="mgnx-20250930.xsd#mgnx_RevenueRemainingPerformanceObligationVariableConsiderationRoyaltyPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4220a067-98e5-483e-a94e-7073411e4c08" xlink:to="loc_mgnx_RevenueRemainingPerformanceObligationVariableConsiderationRoyaltyPercentage_ecbb214f-4dc6-4124-819a-2feca7117bec" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ContractWithCustomerNumberOfMilestonesAchieved_84dbca7b-545f-4e7b-b315-2717f532cc1a" xlink:href="mgnx-20250930.xsd#mgnx_ContractWithCustomerNumberOfMilestonesAchieved"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4220a067-98e5-483e-a94e-7073411e4c08" xlink:to="loc_mgnx_ContractWithCustomerNumberOfMilestonesAchieved_84dbca7b-545f-4e7b-b315-2717f532cc1a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_481935c0-ea2f-4b79-897c-8c983e6ab724" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4220a067-98e5-483e-a94e-7073411e4c08" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_481935c0-ea2f-4b79-897c-8c983e6ab724" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_f144fb83-7380-4d68-a10b-5a94e047b019" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccountsReceivableNetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4220a067-98e5-483e-a94e-7073411e4c08" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_f144fb83-7380-4d68-a10b-5a94e047b019" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/StockBasedCompensationStockBasedCompensationExpenseDetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#StockBasedCompensationStockBasedCompensationExpenseDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/StockBasedCompensationStockBasedCompensationExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3a929204-3b1d-4711-b99d-3b0e0931f65d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_517dd0fe-cffe-4551-86f4-dd9084908945" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3a929204-3b1d-4711-b99d-3b0e0931f65d" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_517dd0fe-cffe-4551-86f4-dd9084908945" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_c533ebb3-4360-420b-a955-ed480c7c0348" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_517dd0fe-cffe-4551-86f4-dd9084908945" xlink:to="loc_us-gaap_PlanNameAxis_c533ebb3-4360-420b-a955-ed480c7c0348" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_c533ebb3-4360-420b-a955-ed480c7c0348_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_c533ebb3-4360-420b-a955-ed480c7c0348" xlink:to="loc_us-gaap_PlanNameDomain_c533ebb3-4360-420b-a955-ed480c7c0348_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_ea15e093-2b9b-4067-99bf-8f38a1af2591" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_c533ebb3-4360-420b-a955-ed480c7c0348" xlink:to="loc_us-gaap_PlanNameDomain_ea15e093-2b9b-4067-99bf-8f38a1af2591" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_TwoThousandSixteenEmployeeStockPurchasePlanMember_ff21e06f-ffd0-4a86-aaa3-b21023acb0e8" xlink:href="mgnx-20250930.xsd#mgnx_TwoThousandSixteenEmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_ea15e093-2b9b-4067-99bf-8f38a1af2591" xlink:to="loc_mgnx_TwoThousandSixteenEmployeeStockPurchasePlanMember_ff21e06f-ffd0-4a86-aaa3-b21023acb0e8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_StockIncentivePlan2023MemberMember_59d4f9af-b59e-4aab-b855-c842ed434380" xlink:href="mgnx-20250930.xsd#mgnx_StockIncentivePlan2023MemberMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_ea15e093-2b9b-4067-99bf-8f38a1af2591" xlink:to="loc_mgnx_StockIncentivePlan2023MemberMember_59d4f9af-b59e-4aab-b855-c842ed434380" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_TwoThousandSixteenEmployeeStockPurchasePlanMemberMember_bfc45e3b-a1cb-4a5e-bc78-bd908e93d2c9" xlink:href="mgnx-20250930.xsd#mgnx_TwoThousandSixteenEmployeeStockPurchasePlanMemberMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_ea15e093-2b9b-4067-99bf-8f38a1af2591" xlink:to="loc_mgnx_TwoThousandSixteenEmployeeStockPurchasePlanMemberMember_bfc45e3b-a1cb-4a5e-bc78-bd908e93d2c9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_3507bc92-ca7e-42da-aa03-09bd39bbd667" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3a929204-3b1d-4711-b99d-3b0e0931f65d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_3507bc92-ca7e-42da-aa03-09bd39bbd667" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_5d566daa-4898-4b36-b3ee-ce7c8745e847" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3a929204-3b1d-4711-b99d-3b0e0931f65d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_5d566daa-4898-4b36-b3ee-ce7c8745e847" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOfferingPeriod_bc1b55ad-d4cb-4cc4-9d8f-14e010a9dc43" xlink:href="mgnx-20250930.xsd#mgnx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOfferingPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3a929204-3b1d-4711-b99d-3b0e0931f65d" xlink:to="loc_mgnx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOfferingPeriod_bc1b55ad-d4cb-4cc4-9d8f-14e010a9dc43" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_47dbb322-b648-4e65-80cd-20fd4a434e4f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3a929204-3b1d-4711-b99d-3b0e0931f65d" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_47dbb322-b648-4e65-80cd-20fd4a434e4f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_1ddf3ed9-1a7b-4580-a4f4-109fafe6fd10" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3a929204-3b1d-4711-b99d-3b0e0931f65d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_1ddf3ed9-1a7b-4580-a4f4-109fafe6fd10" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_3773b1ae-30a6-420b-be22-efa6dd3f8677" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3a929204-3b1d-4711-b99d-3b0e0931f65d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_3773b1ae-30a6-420b-be22-efa6dd3f8677" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_0a2e8f39-7a1f-40d4-8bd2-bcbf80731621" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3a929204-3b1d-4711-b99d-3b0e0931f65d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_0a2e8f39-7a1f-40d4-8bd2-bcbf80731621" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_0ba565e4-e50f-4e65-9e42-40f6b9fe3a62" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_8d90a6e1-9ec7-4446-bbf4-be933b0751ef" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_0ba565e4-e50f-4e65-9e42-40f6b9fe3a62" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_8d90a6e1-9ec7-4446-bbf4-be933b0751ef" xlink:type="arc" order="2" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_5307d39b-f82d-4834-9db8-63781fdf4140" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_8d90a6e1-9ec7-4446-bbf4-be933b0751ef" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_5307d39b-f82d-4834-9db8-63781fdf4140" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_5307d39b-f82d-4834-9db8-63781fdf4140_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_5307d39b-f82d-4834-9db8-63781fdf4140" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_5307d39b-f82d-4834-9db8-63781fdf4140_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_335db698-2e4a-4051-92a1-e082f8cf708f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_5307d39b-f82d-4834-9db8-63781fdf4140" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_335db698-2e4a-4051-92a1-e082f8cf708f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_6d6748ac-f02f-4636-ac5b-22483f12e91b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_335db698-2e4a-4051-92a1-e082f8cf708f" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_6d6748ac-f02f-4636-ac5b-22483f12e91b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpenseMember_4c8a52d7-32b0-41e2-b7ad-3e0aae3a59cc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GeneralAndAdministrativeExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_335db698-2e4a-4051-92a1-e082f8cf708f" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpenseMember_4c8a52d7-32b0-41e2-b7ad-3e0aae3a59cc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_e6289cdc-5d8e-4d9d-bc90-d21c76cf920b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_0ba565e4-e50f-4e65-9e42-40f6b9fe3a62" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_e6289cdc-5d8e-4d9d-bc90-d21c76cf920b" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/StockBasedCompensationOptionPricingAssumptionsDetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#StockBasedCompensationOptionPricingAssumptionsDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/StockBasedCompensationOptionPricingAssumptionsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_dc4198c6-17bc-4a6c-9b9f-b547bd91d59b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_12d25498-1b56-4f35-8cf7-43e08a8a1dea" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_dc4198c6-17bc-4a6c-9b9f-b547bd91d59b" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_12d25498-1b56-4f35-8cf7-43e08a8a1dea" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_2f41f867-620e-4e1f-afc2-05fd543f8951" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_12d25498-1b56-4f35-8cf7-43e08a8a1dea" xlink:to="loc_srt_RangeAxis_2f41f867-620e-4e1f-afc2-05fd543f8951" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_2f41f867-620e-4e1f-afc2-05fd543f8951_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_2f41f867-620e-4e1f-afc2-05fd543f8951" xlink:to="loc_srt_RangeMember_2f41f867-620e-4e1f-afc2-05fd543f8951_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_c6e1bf0e-3f06-4283-be38-8ae9a6701ac2" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_2f41f867-620e-4e1f-afc2-05fd543f8951" xlink:to="loc_srt_RangeMember_c6e1bf0e-3f06-4283-be38-8ae9a6701ac2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_538a3254-9a1e-4169-9da9-f8af3a7078c7" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_c6e1bf0e-3f06-4283-be38-8ae9a6701ac2" xlink:to="loc_srt_MinimumMember_538a3254-9a1e-4169-9da9-f8af3a7078c7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_58a10590-3f95-4da0-9101-6b8db42b5cfb" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_c6e1bf0e-3f06-4283-be38-8ae9a6701ac2" xlink:to="loc_srt_MaximumMember_58a10590-3f95-4da0-9101-6b8db42b5cfb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_cb00be21-76e5-43ed-a386-d2890fdc361f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_dc4198c6-17bc-4a6c-9b9f-b547bd91d59b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_cb00be21-76e5-43ed-a386-d2890fdc361f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_40fa24fe-382a-4eed-8080-2b5211c81249" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_dc4198c6-17bc-4a6c-9b9f-b547bd91d59b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_40fa24fe-382a-4eed-8080-2b5211c81249" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_a269a30b-2ba3-4a13-a087-707fa613b7e6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_dc4198c6-17bc-4a6c-9b9f-b547bd91d59b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_a269a30b-2ba3-4a13-a087-707fa613b7e6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_7bde3d36-9f69-4754-a649-58bad9bc75eb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_dc4198c6-17bc-4a6c-9b9f-b547bd91d59b" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_7bde3d36-9f69-4754-a649-58bad9bc75eb" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/StockbasedCompensationRestrictedStockUnitActivityDetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#StockbasedCompensationRestrictedStockUnitActivityDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/StockbasedCompensationRestrictedStockUnitActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_00e90c0f-79a9-4fda-b635-69047724614a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_da031ca6-ebf3-477a-894b-40b26fbf413c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_00e90c0f-79a9-4fda-b635-69047724614a" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_da031ca6-ebf3-477a-894b-40b26fbf413c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_a8c0c9eb-2e11-4e8a-806f-e5402c9a9d67" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_da031ca6-ebf3-477a-894b-40b26fbf413c" xlink:to="loc_us-gaap_AwardTypeAxis_a8c0c9eb-2e11-4e8a-806f-e5402c9a9d67" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a8c0c9eb-2e11-4e8a-806f-e5402c9a9d67_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_a8c0c9eb-2e11-4e8a-806f-e5402c9a9d67" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a8c0c9eb-2e11-4e8a-806f-e5402c9a9d67_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_d5936190-a41c-44f4-82fe-6d120ffbbab7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_a8c0c9eb-2e11-4e8a-806f-e5402c9a9d67" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_d5936190-a41c-44f4-82fe-6d120ffbbab7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_9d9497e7-5df7-402f-9d25-3a0c591850d3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_d5936190-a41c-44f4-82fe-6d120ffbbab7" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_9d9497e7-5df7-402f-9d25-3a0c591850d3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_feb815b3-6db6-4c08-9374-073cf989d624" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_00e90c0f-79a9-4fda-b635-69047724614a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_feb815b3-6db6-4c08-9374-073cf989d624" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_9cf0fe07-85ec-4ccd-af61-14e6ffbf78dd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_feb815b3-6db6-4c08-9374-073cf989d624" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_9cf0fe07-85ec-4ccd-af61-14e6ffbf78dd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_d9ae9a31-861c-4299-84e7-697d0c73ba8c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_feb815b3-6db6-4c08-9374-073cf989d624" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_d9ae9a31-861c-4299-84e7-697d0c73ba8c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_6be8718c-373c-453b-8511-71b7184b0a23" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_feb815b3-6db6-4c08-9374-073cf989d624" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_6be8718c-373c-453b-8511-71b7184b0a23" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_fd34556c-22da-4aac-9108-7a2a0859b4e5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_feb815b3-6db6-4c08-9374-073cf989d624" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_fd34556c-22da-4aac-9108-7a2a0859b4e5" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_a2803e99-e44d-4fce-a288-a19dab54f7ab" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_feb815b3-6db6-4c08-9374-073cf989d624" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_a2803e99-e44d-4fce-a288-a19dab54f7ab" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_de8fa4a0-b008-487a-b90b-4808aa4de841" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_4f1efb32-63a2-4853-a1f0-f9070c1a8571" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_00e90c0f-79a9-4fda-b635-69047724614a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_4f1efb32-63a2-4853-a1f0-f9070c1a8571" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_719b0519-2bc3-4a48-8209-f06ff93db4ba" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_4f1efb32-63a2-4853-a1f0-f9070c1a8571" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_719b0519-2bc3-4a48-8209-f06ff93db4ba" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_47ffb56a-f178-474c-8107-52c9bd8b969d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_4f1efb32-63a2-4853-a1f0-f9070c1a8571" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_47ffb56a-f178-474c-8107-52c9bd8b969d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_1ab12955-b0aa-498b-91be-aa96f7846f2d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_4f1efb32-63a2-4853-a1f0-f9070c1a8571" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_1ab12955-b0aa-498b-91be-aa96f7846f2d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_2245e97f-976a-4716-85c8-30575d2fcb9b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_f46508df-3148-4da6-9dbd-e237b8713eee" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_00e90c0f-79a9-4fda-b635-69047724614a" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_f46508df-3148-4da6-9dbd-e237b8713eee" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_7e5d9a50-d0c0-4c7e-9981-c8c8aa475d8f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_00e90c0f-79a9-4fda-b635-69047724614a" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_7e5d9a50-d0c0-4c7e-9981-c8c8aa475d8f" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/InLicensingArrangementDetail" xlink:type="simple" xlink:href="mgnx-20250930.xsd#InLicensingArrangementDetail"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/InLicensingArrangementDetail" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_InLicensingArrangementLineItems_ddf2499b-ac5d-4bc4-bfdb-ee2a1463b3f8" xlink:href="mgnx-20250930.xsd#mgnx_InLicensingArrangementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_InLicensingArrangementTable_879d0022-7e00-4332-9e3b-57d3a6cb58dc" xlink:href="mgnx-20250930.xsd#mgnx_InLicensingArrangementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_mgnx_InLicensingArrangementLineItems_ddf2499b-ac5d-4bc4-bfdb-ee2a1463b3f8" xlink:to="loc_mgnx_InLicensingArrangementTable_879d0022-7e00-4332-9e3b-57d3a6cb58dc" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_2cde1a1f-5ec2-4092-ac0d-703138ad9c76" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_mgnx_InLicensingArrangementTable_879d0022-7e00-4332-9e3b-57d3a6cb58dc" xlink:to="loc_srt_CounterpartyNameAxis_2cde1a1f-5ec2-4092-ac0d-703138ad9c76" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_2cde1a1f-5ec2-4092-ac0d-703138ad9c76_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_2cde1a1f-5ec2-4092-ac0d-703138ad9c76" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_2cde1a1f-5ec2-4092-ac0d-703138ad9c76_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_ff47fca6-8838-48dc-a5f4-02cc49e006f7" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_2cde1a1f-5ec2-4092-ac0d-703138ad9c76" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_ff47fca6-8838-48dc-a5f4-02cc49e006f7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_SynaffixBVMember_9be27957-829a-4d5c-9433-5ded3b52ea93" xlink:href="mgnx-20250930.xsd#mgnx_SynaffixBVMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_ff47fca6-8838-48dc-a5f4-02cc49e006f7" xlink:to="loc_mgnx_SynaffixBVMember_9be27957-829a-4d5c-9433-5ded3b52ea93" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_07af2a29-d2a6-4785-8aa1-b3b44ed21df7" xlink:href="mgnx-20250930.xsd#mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_InLicensingArrangementLineItems_ddf2499b-ac5d-4bc4-bfdb-ee2a1463b3f8" xlink:to="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_07af2a29-d2a6-4785-8aa1-b3b44ed21df7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_868377a7-c4f6-4921-8ee8-60e5b67461c7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_InLicensingArrangementLineItems_ddf2499b-ac5d-4bc4-bfdb-ee2a1463b3f8" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_868377a7-c4f6-4921-8ee8-60e5b67461c7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractualObligation_e9fb7110-634d-4c55-9e09-9263b00c42e3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractualObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_InLicensingArrangementLineItems_ddf2499b-ac5d-4bc4-bfdb-ee2a1463b3f8" xlink:to="loc_us-gaap_ContractualObligation_e9fb7110-634d-4c55-9e09-9263b00c42e3" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/SegmentReportingDetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#SegmentReportingDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/SegmentReportingDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingReconcilingItemForOperatingProfitLossFromSegmentToConsolidatedLineItems_5f6dd679-7d84-45db-8e63-d0dc59780380" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentReportingReconcilingItemForOperatingProfitLossFromSegmentToConsolidatedLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReconciliationOfOperatingProfitLossFromSegmentsToConsolidatedTable_e5db75f9-3507-4337-b29a-6b1d218e8d07" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ReconciliationOfOperatingProfitLossFromSegmentsToConsolidatedTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingReconcilingItemForOperatingProfitLossFromSegmentToConsolidatedLineItems_5f6dd679-7d84-45db-8e63-d0dc59780380" xlink:to="loc_us-gaap_ReconciliationOfOperatingProfitLossFromSegmentsToConsolidatedTable_e5db75f9-3507-4337-b29a-6b1d218e8d07" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CapitalizedCostsOfUnprovedPropertiesExcludedFromAmortizationByPropertyOrProjectAxis_9bb06bcc-26ad-4a06-9791-37427ada0ec7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CapitalizedCostsOfUnprovedPropertiesExcludedFromAmortizationByPropertyOrProjectAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ReconciliationOfOperatingProfitLossFromSegmentsToConsolidatedTable_e5db75f9-3507-4337-b29a-6b1d218e8d07" xlink:to="loc_us-gaap_CapitalizedCostsOfUnprovedPropertiesExcludedFromAmortizationByPropertyOrProjectAxis_9bb06bcc-26ad-4a06-9791-37427ada0ec7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProjectMember_9bb06bcc-26ad-4a06-9791-37427ada0ec7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProjectMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CapitalizedCostsOfUnprovedPropertiesExcludedFromAmortizationByPropertyOrProjectAxis_9bb06bcc-26ad-4a06-9791-37427ada0ec7" xlink:to="loc_us-gaap_ProjectMember_9bb06bcc-26ad-4a06-9791-37427ada0ec7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProjectMember_9f8ad1c3-1078-4338-94c9-bb694bc73715" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProjectMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CapitalizedCostsOfUnprovedPropertiesExcludedFromAmortizationByPropertyOrProjectAxis_9bb06bcc-26ad-4a06-9791-37427ada0ec7" xlink:to="loc_us-gaap_ProjectMember_9f8ad1c3-1078-4338-94c9-bb694bc73715" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_LorigerlimabMember_6ba28a9f-db49-4d21-9269-8dc1691f0da6" xlink:href="mgnx-20250930.xsd#mgnx_LorigerlimabMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProjectMember_9f8ad1c3-1078-4338-94c9-bb694bc73715" xlink:to="loc_mgnx_LorigerlimabMember_6ba28a9f-db49-4d21-9269-8dc1691f0da6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_MGC030Member_c418b7b3-874a-4a24-b6c9-06c3a3f80dcf" xlink:href="mgnx-20250930.xsd#mgnx_MGC030Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProjectMember_9f8ad1c3-1078-4338-94c9-bb694bc73715" xlink:to="loc_mgnx_MGC030Member_c418b7b3-874a-4a24-b6c9-06c3a3f80dcf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_MGC028Member_d266d595-b3b2-4e28-ad2e-4275af745294" xlink:href="mgnx-20250930.xsd#mgnx_MGC028Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProjectMember_9f8ad1c3-1078-4338-94c9-bb694bc73715" xlink:to="loc_mgnx_MGC028Member_d266d595-b3b2-4e28-ad2e-4275af745294" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_VobramitanmabDuocarmazineMember_26d3ec5a-b5e5-427a-8a34-80c8516adef9" xlink:href="mgnx-20250930.xsd#mgnx_VobramitanmabDuocarmazineMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProjectMember_9f8ad1c3-1078-4338-94c9-bb694bc73715" xlink:to="loc_mgnx_VobramitanmabDuocarmazineMember_26d3ec5a-b5e5-427a-8a34-80c8516adef9" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NextGenerationTCellEngagersMember_2eb09fc5-aca6-4845-9039-0d614f3e2165" xlink:href="mgnx-20250930.xsd#mgnx_NextGenerationTCellEngagersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProjectMember_9f8ad1c3-1078-4338-94c9-bb694bc73715" xlink:to="loc_mgnx_NextGenerationTCellEngagersMember_2eb09fc5-aca6-4845-9039-0d614f3e2165" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_MGC026Member_0c2e6b10-243c-41d9-b66f-d76e780a7e07" xlink:href="mgnx-20250930.xsd#mgnx_MGC026Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProjectMember_9f8ad1c3-1078-4338-94c9-bb694bc73715" xlink:to="loc_mgnx_MGC026Member_0c2e6b10-243c-41d9-b66f-d76e780a7e07" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_MGD024Member_9de9a761-cb27-4c32-83d1-a6afaa7dfbb0" xlink:href="mgnx-20250930.xsd#mgnx_MGD024Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProjectMember_9f8ad1c3-1078-4338-94c9-bb694bc73715" xlink:to="loc_mgnx_MGD024Member_9de9a761-cb27-4c32-83d1-a6afaa7dfbb0" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ADCMember_ea977c13-7657-4a3c-9a94-a3a575e6e076" xlink:href="mgnx-20250930.xsd#mgnx_ADCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProjectMember_9f8ad1c3-1078-4338-94c9-bb694bc73715" xlink:to="loc_mgnx_ADCMember_ea977c13-7657-4a3c-9a94-a3a575e6e076" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_MargetuximabMember_f888d9ee-8d98-41e0-b245-305f2ef4d13b" xlink:href="mgnx-20250930.xsd#mgnx_MargetuximabMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProjectMember_9f8ad1c3-1078-4338-94c9-bb694bc73715" xlink:to="loc_mgnx_MargetuximabMember_f888d9ee-8d98-41e0-b245-305f2ef4d13b" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_OtherProgramsMember_c050bcbb-7252-45c4-b53e-b1745a880a82" xlink:href="mgnx-20250930.xsd#mgnx_OtherProgramsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProjectMember_9f8ad1c3-1078-4338-94c9-bb694bc73715" xlink:to="loc_mgnx_OtherProgramsMember_c050bcbb-7252-45c4-b53e-b1745a880a82" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_884da80c-9518-4712-a461-87772c2d7e98" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ReconciliationOfOperatingProfitLossFromSegmentsToConsolidatedTable_e5db75f9-3507-4337-b29a-6b1d218e8d07" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_884da80c-9518-4712-a461-87772c2d7e98" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_884da80c-9518-4712-a461-87772c2d7e98_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_884da80c-9518-4712-a461-87772c2d7e98" xlink:to="loc_us-gaap_SegmentDomain_884da80c-9518-4712-a461-87772c2d7e98_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_42c90bd7-216b-45f7-b362-e88867b3a622" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_884da80c-9518-4712-a461-87772c2d7e98" xlink:to="loc_us-gaap_SegmentDomain_42c90bd7-216b-45f7-b362-e88867b3a622" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_MainSegmentMember_2a7c17dc-3de7-4925-8d6d-9f6c9e925c09" xlink:href="mgnx-20250930.xsd#mgnx_MainSegmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_42c90bd7-216b-45f7-b362-e88867b3a622" xlink:to="loc_mgnx_MainSegmentMember_2a7c17dc-3de7-4925-8d6d-9f6c9e925c09" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_63fc01f8-ecc3-4959-aa20-b2ab35e5f20d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingReconcilingItemForOperatingProfitLossFromSegmentToConsolidatedLineItems_5f6dd679-7d84-45db-8e63-d0dc59780380" xlink:to="loc_us-gaap_Revenues_63fc01f8-ecc3-4959-aa20-b2ab35e5f20d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_a3485001-ca40-4125-a9c8-87dffe455700" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingReconcilingItemForOperatingProfitLossFromSegmentToConsolidatedLineItems_5f6dd679-7d84-45db-8e63-d0dc59780380" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_a3485001-ca40-4125-a9c8-87dffe455700" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CostOfManufacturingServices_65e8b270-5fca-4d87-a18b-860ea12e0f86" xlink:href="mgnx-20250930.xsd#mgnx_CostOfManufacturingServices"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingReconcilingItemForOperatingProfitLossFromSegmentToConsolidatedLineItems_5f6dd679-7d84-45db-8e63-d0dc59780380" xlink:to="loc_mgnx_CostOfManufacturingServices_65e8b270-5fca-4d87-a18b-860ea12e0f86" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_25080880-574c-43b7-bdbd-e7beb09e36d7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingReconcilingItemForOperatingProfitLossFromSegmentToConsolidatedLineItems_5f6dd679-7d84-45db-8e63-d0dc59780380" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_25080880-574c-43b7-bdbd-e7beb09e36d7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_cbe6b21e-2223-47af-8152-b720e9b120b8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingReconcilingItemForOperatingProfitLossFromSegmentToConsolidatedLineItems_5f6dd679-7d84-45db-8e63-d0dc59780380" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_cbe6b21e-2223-47af-8152-b720e9b120b8" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingOtherItemAmount_2884766f-b1d6-4587-b8c7-0b1d59a4c73f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentReportingOtherItemAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingReconcilingItemForOperatingProfitLossFromSegmentToConsolidatedLineItems_5f6dd679-7d84-45db-8e63-d0dc59780380" xlink:to="loc_us-gaap_SegmentReportingOtherItemAmount_2884766f-b1d6-4587-b8c7-0b1d59a4c73f" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_1cc0383b-c61a-40e8-afda-14658720b1e7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingReconcilingItemForOperatingProfitLossFromSegmentToConsolidatedLineItems_5f6dd679-7d84-45db-8e63-d0dc59780380" xlink:to="loc_us-gaap_NetIncomeLoss_1cc0383b-c61a-40e8-afda-14658720b1e7" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/SubsequentEventDetails" xlink:type="simple" xlink:href="mgnx-20250930.xsd#SubsequentEventDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/SubsequentEventDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventLineItems_85ab9de0-df71-4f56-9962-97cd64c85098" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsequentEventLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTable_b2a43a56-e1d1-40d9-90ec-b890b0bdef98" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsequentEventTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsequentEventLineItems_85ab9de0-df71-4f56-9962-97cd64c85098" xlink:to="loc_us-gaap_SubsequentEventTable_b2a43a56-e1d1-40d9-90ec-b890b0bdef98" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_67375143-91e7-48e9-8db9-fa05c1c70a06" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_b2a43a56-e1d1-40d9-90ec-b890b0bdef98" xlink:to="loc_srt_CounterpartyNameAxis_67375143-91e7-48e9-8db9-fa05c1c70a06" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_67375143-91e7-48e9-8db9-fa05c1c70a06_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_67375143-91e7-48e9-8db9-fa05c1c70a06" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_67375143-91e7-48e9-8db9-fa05c1c70a06_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_345105ff-25eb-4b52-bfec-fa2198299a9d" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_67375143-91e7-48e9-8db9-fa05c1c70a06" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_345105ff-25eb-4b52-bfec-fa2198299a9d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_GileadMember_7b031029-985a-4b63-b05f-a1f50d214d03" xlink:href="mgnx-20250930.xsd#mgnx_GileadMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_345105ff-25eb-4b52-bfec-fa2198299a9d" xlink:to="loc_mgnx_GileadMember_7b031029-985a-4b63-b05f-a1f50d214d03" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_6c47a599-eee0-471b-ad9e-93abf8706b33" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsequentEventTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_b2a43a56-e1d1-40d9-90ec-b890b0bdef98" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_6c47a599-eee0-471b-ad9e-93abf8706b33" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_6c47a599-eee0-471b-ad9e-93abf8706b33_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_6c47a599-eee0-471b-ad9e-93abf8706b33" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_6c47a599-eee0-471b-ad9e-93abf8706b33_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_d430bf80-475f-4294-b88c-0e87b12818b7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_6c47a599-eee0-471b-ad9e-93abf8706b33" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_d430bf80-475f-4294-b88c-0e87b12818b7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_e18da348-ff66-446f-b60a-6a88d299af3b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsequentEventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_d430bf80-475f-4294-b88c-0e87b12818b7" xlink:to="loc_us-gaap_SubsequentEventMember_e18da348-ff66-446f-b60a-6a88d299af3b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_7708a345-4fd3-442a-a85e-63fb6e1a2f9a" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_b2a43a56-e1d1-40d9-90ec-b890b0bdef98" xlink:to="loc_srt_ProductOrServiceAxis_7708a345-4fd3-442a-a85e-63fb6e1a2f9a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_7708a345-4fd3-442a-a85e-63fb6e1a2f9a_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_7708a345-4fd3-442a-a85e-63fb6e1a2f9a" xlink:to="loc_srt_ProductsAndServicesDomain_7708a345-4fd3-442a-a85e-63fb6e1a2f9a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_f93ea72a-2fe2-4223-a982-7237dce952ab" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_7708a345-4fd3-442a-a85e-63fb6e1a2f9a" xlink:to="loc_srt_ProductsAndServicesDomain_f93ea72a-2fe2-4223-a982-7237dce952ab" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LicenseMember_d09b4a14-58a0-4c6c-b4ca-69e002f25e60" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LicenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_f93ea72a-2fe2-4223-a982-7237dce952ab" xlink:to="loc_us-gaap_LicenseMember_d09b4a14-58a0-4c6c-b4ca-69e002f25e60" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligation_95eb0ba8-d6a3-4ca0-93de-003f5e9f60fa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_85ab9de0-df71-4f56-9962-97cd64c85098" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligation_95eb0ba8-d6a3-4ca0-93de-003f5e9f60fa" xlink:type="arc" order="0"/>
  </link:definitionLink>
</link:linkbase>
