Macrophages play a critical role in tumor immunity and immunotherapy. Tumor-associated macrophages (TAMs) are generally associated with poor prognosis in solid tumors, as they suppress T cell responses and promote tumor growth. TAMs can be influenced by microenvironmental cues such as hypoxia and fibrosis, which shift their phenotypes toward immunosuppression. Recent studies have shown that targeting TAMs can enhance the efficacy of immunotherapy, including checkpoint blockade. Clinical trials are now evaluating the combination of TAM targeting with immunotherapy. Macrophages are diverse cells with varying functions depending on their origin, tissue of residence, and microenvironmental cues. They can be classified into M1 and M2 phenotypes, but recent research suggests that macrophage activation states form a continuum of phenotypes. TAMs can originate from embryonic precursors or monocytes, and their functions can differ based on their origin. In tumors, TAMs often derive from circulating monocytes, but some studies suggest that tissue-resident macrophages may also contribute. Tumor hypoxia and fibrosis significantly influence TAM function. Hypoxia can induce the production of factors that recruit TAMs to hypoxic regions, while fibrosis can alter the extracellular matrix and influence TAM phenotypes. TAMs can also be influenced by factors such as lactic acid and pH, which can affect their immunosuppressive activity. Lymphocytes, including T cells and regulatory T cells, can influence TAM function and tumor immunity. T helper 1 (Th1) cells and natural killer (NK) cells can promote an anti-tumor phenotype in TAMs, while Th2 cells and regulatory T cells can promote immunosuppression. TAMs can also suppress T cell responses through the production of cytokines such as IL-10 and TGF-β. TAMs can directly suppress T cell function through mechanisms such as arginase-1 activity, iNOS expression, and PD-L1/PD-1 signaling. They can also indirectly suppress T cell responses by regulating vascular adhesion molecules, producing peroxynitrites, and influencing the tumor microenvironment. TAMs can also influence T cell recruitment and localization within tumors. Therapeutic targeting of TAMs is being explored as a strategy to enhance immunotherapy. Approaches include depleting TAMs through CSF1R or CCR2 inhibition, or reprogramming TAMs toward an anti-tumor phenotype using agonist CD40 antibodies or epigenetic reprogramming. These strategies are being evaluated in clinical trials, with some showing promising results in combination with immunotherapy. Despite these advances, challenges remain in translating TAM-targeting strategies to clinical practice. The optimal therapeutic approach is not yet clear, and further research is needed to understand the complex interactions between TAMs and the tumor microenvironment. The role of TAMs in cancer varies across tumor types, and their function can be influenced byMacrophages play a critical role in tumor immunity and immunotherapy. Tumor-associated macrophages (TAMs) are generally associated with poor prognosis in solid tumors, as they suppress T cell responses and promote tumor growth. TAMs can be influenced by microenvironmental cues such as hypoxia and fibrosis, which shift their phenotypes toward immunosuppression. Recent studies have shown that targeting TAMs can enhance the efficacy of immunotherapy, including checkpoint blockade. Clinical trials are now evaluating the combination of TAM targeting with immunotherapy. Macrophages are diverse cells with varying functions depending on their origin, tissue of residence, and microenvironmental cues. They can be classified into M1 and M2 phenotypes, but recent research suggests that macrophage activation states form a continuum of phenotypes. TAMs can originate from embryonic precursors or monocytes, and their functions can differ based on their origin. In tumors, TAMs often derive from circulating monocytes, but some studies suggest that tissue-resident macrophages may also contribute. Tumor hypoxia and fibrosis significantly influence TAM function. Hypoxia can induce the production of factors that recruit TAMs to hypoxic regions, while fibrosis can alter the extracellular matrix and influence TAM phenotypes. TAMs can also be influenced by factors such as lactic acid and pH, which can affect their immunosuppressive activity. Lymphocytes, including T cells and regulatory T cells, can influence TAM function and tumor immunity. T helper 1 (Th1) cells and natural killer (NK) cells can promote an anti-tumor phenotype in TAMs, while Th2 cells and regulatory T cells can promote immunosuppression. TAMs can also suppress T cell responses through the production of cytokines such as IL-10 and TGF-β. TAMs can directly suppress T cell function through mechanisms such as arginase-1 activity, iNOS expression, and PD-L1/PD-1 signaling. They can also indirectly suppress T cell responses by regulating vascular adhesion molecules, producing peroxynitrites, and influencing the tumor microenvironment. TAMs can also influence T cell recruitment and localization within tumors. Therapeutic targeting of TAMs is being explored as a strategy to enhance immunotherapy. Approaches include depleting TAMs through CSF1R or CCR2 inhibition, or reprogramming TAMs toward an anti-tumor phenotype using agonist CD40 antibodies or epigenetic reprogramming. These strategies are being evaluated in clinical trials, with some showing promising results in combination with immunotherapy. Despite these advances, challenges remain in translating TAM-targeting strategies to clinical practice. The optimal therapeutic approach is not yet clear, and further research is needed to understand the complex interactions between TAMs and the tumor microenvironment. The role of TAMs in cancer varies across tumor types, and their function can be influenced by