<p>Triple-negative breast cancer (TNBC) presents significant clinical challenges due to its high invasiveness, heterogeneity, and lack of effective targeted therapies. While chemotherapy remains the primary treatment modality, its efficacy is often limited by the emergence of drug resistance. To address these limitations, we developed a biomimetic, macrophage membrane-camouflaged nanoplatform based on Fe-TCPP metal–organic frameworks (MOFs) for targeted, synergistic chemo-ferroptotic therapy of TNBC. The porous Fe-TCPP MOFs serve as both drug carriers, enabling efficient cisplatin loading, and ferroptosis related modulators, promoting intracellular Fe²⁺ accumulation, enhancing the Fenton reaction, and depleting glutathione (GSH) to trigger lipid peroxidation and oxidative cell death. The macrophage membrane coating imparts immune evasion and tumor-targeting capabilities, prolonging systemic circulation and favoring preferential accumulation at tumor sites. In vitro and in vivo studies demonstrate that this macrophage membrane-coated nanotherapeutic significantly enhances cisplatin sensitivity, reduces drug resistance, and achieves potent antitumor efficacy in TNBC models. This work presents a promising strategy that integrates ferroptosis related oxidative stress with chemotherapy, offering a potential pathway to overcome therapeutic resistance and improve the safety and effectiveness of TNBC treatment.</p> Graphical Abstract <p></p>