The article reviews the role of macrophages in cancer development, metastasis, and immunotherapy. Macrophages, which originate from monocytes and are a key component of the tumor microenvironment (TME), can promote tumor growth, invasion, and metastasis by regulating programmed cell death ligand 1 (PD-L1) expression and interacting with other immune cells. However, when activated properly, macrophages can also play an anti-tumor role by enhancing phagocytosis and cytotoxicity of tumor cells. Tumor-associated macrophages (TAMs) are associated with poor prognosis and drug resistance in patients treated with immunotherapy, making them attractive targets for combined therapy. The combination of TAM targeting and immunotherapy has shown promising results in overcoming drug resistance and improving treatment outcomes in some cancers. The article discusses the origin, polarization, and functions of macrophages, their roles in promoting tumor progression, and their interactions with anti-PD-1/PD-L1 immunotherapy. It also explores strategies for depleting and reprogramming TAMs, including the use of CSF1/CSF1R inhibitors, CCR2 inhibitors, and genetic engineering to reprogram macrophages. The combination of TAM targeting and anti-PD-1 therapy is highlighted as a promising strategy to overcome drug resistance in cancer treatment.The article reviews the role of macrophages in cancer development, metastasis, and immunotherapy. Macrophages, which originate from monocytes and are a key component of the tumor microenvironment (TME), can promote tumor growth, invasion, and metastasis by regulating programmed cell death ligand 1 (PD-L1) expression and interacting with other immune cells. However, when activated properly, macrophages can also play an anti-tumor role by enhancing phagocytosis and cytotoxicity of tumor cells. Tumor-associated macrophages (TAMs) are associated with poor prognosis and drug resistance in patients treated with immunotherapy, making them attractive targets for combined therapy. The combination of TAM targeting and immunotherapy has shown promising results in overcoming drug resistance and improving treatment outcomes in some cancers. The article discusses the origin, polarization, and functions of macrophages, their roles in promoting tumor progression, and their interactions with anti-PD-1/PD-L1 immunotherapy. It also explores strategies for depleting and reprogramming TAMs, including the use of CSF1/CSF1R inhibitors, CCR2 inhibitors, and genetic engineering to reprogram macrophages. The combination of TAM targeting and anti-PD-1 therapy is highlighted as a promising strategy to overcome drug resistance in cancer treatment.