The tumor microenvironment (TME) plays a crucial role in tumor development, metastasis, and immune evasion. Targeted therapy based on TME components, pathways, and active molecules has gained significant attention. Biomimetic nanocarriers, with their low clearance, low immunogenicity, and high targeting efficiency, show great potential in tumor treatment. This review introduces the composition and characteristics of the TME, including cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), tumor blood vessels, and non-tumor cells. It also discusses the latest research progress on biomimetic nanoparticles (NPs) based on TME and their clinical translation opportunities and challenges. The TME is a complex system comprising various cellular and non-cellular components. CAFs, which account for 50% of tumor cells, are essential stromal cells that exhibit unique morphological and functional changes compared to normal fibroblasts. ECM, composed of collagen, elastin, and proteoglycans, provides physical support and regulates cell functions. Tumor blood vessels, different from those in normal tissues, are structurally altered and play a pivotal role in angiogenesis and tumor growth. Non-tumor cells, such as immune cells, include tumor-associated macrophages (TAMs), dendritic cells (DCs), T-cells, B-cells, natural killer (NK) cells, and myeloid-derived suppressor cells (MDSCs), which can either promote or inhibit tumor progression. Biomimetic NPs, modified with cell membranes, exosomes, or other protein molecules, can avoid clearance by the mononuclear phagocytic system, enhancing their therapeutic efficacy. These NPs can deliver targeted anti-tumor drugs, improve drug solubility and bioavailability, and reduce toxic side effects. However, challenges remain in clinical translation, including particle size, surface modification, and immune response induction. The review highlights the application of membrane-coated NPs, such as erythrocyte, tumor cell, and immune cell membranes, in targeting and modulating the TME. These NPs exhibit good biocompatibility, targeting ability, and low immunogenicity, making them suitable for delivering anti-tumor drugs and improving treatment outcomes. The review also discusses the use of biomimetic NPs in phototherapy, photodynamic therapy, and cancer immunotherapy, emphasizing their potential in overcoming the immunosuppressive state caused by tumors. In conclusion, biomimetic NPs offer promising strategies for targeting and modulating the TME, but further research is needed to address challenges in clinical translation and optimize their therapeutic efficacy.The tumor microenvironment (TME) plays a crucial role in tumor development, metastasis, and immune evasion. Targeted therapy based on TME components, pathways, and active molecules has gained significant attention. Biomimetic nanocarriers, with their low clearance, low immunogenicity, and high targeting efficiency, show great potential in tumor treatment. This review introduces the composition and characteristics of the TME, including cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), tumor blood vessels, and non-tumor cells. It also discusses the latest research progress on biomimetic nanoparticles (NPs) based on TME and their clinical translation opportunities and challenges. The TME is a complex system comprising various cellular and non-cellular components. CAFs, which account for 50% of tumor cells, are essential stromal cells that exhibit unique morphological and functional changes compared to normal fibroblasts. ECM, composed of collagen, elastin, and proteoglycans, provides physical support and regulates cell functions. Tumor blood vessels, different from those in normal tissues, are structurally altered and play a pivotal role in angiogenesis and tumor growth. Non-tumor cells, such as immune cells, include tumor-associated macrophages (TAMs), dendritic cells (DCs), T-cells, B-cells, natural killer (NK) cells, and myeloid-derived suppressor cells (MDSCs), which can either promote or inhibit tumor progression. Biomimetic NPs, modified with cell membranes, exosomes, or other protein molecules, can avoid clearance by the mononuclear phagocytic system, enhancing their therapeutic efficacy. These NPs can deliver targeted anti-tumor drugs, improve drug solubility and bioavailability, and reduce toxic side effects. However, challenges remain in clinical translation, including particle size, surface modification, and immune response induction. The review highlights the application of membrane-coated NPs, such as erythrocyte, tumor cell, and immune cell membranes, in targeting and modulating the TME. These NPs exhibit good biocompatibility, targeting ability, and low immunogenicity, making them suitable for delivering anti-tumor drugs and improving treatment outcomes. The review also discusses the use of biomimetic NPs in phototherapy, photodynamic therapy, and cancer immunotherapy, emphasizing their potential in overcoming the immunosuppressive state caused by tumors. In conclusion, biomimetic NPs offer promising strategies for targeting and modulating the TME, but further research is needed to address challenges in clinical translation and optimize their therapeutic efficacy.