Tumor-associated macrophages (TAMs) play a critical role in tumor progression by promoting genetic instability, nurturing cancer stem cells, facilitating metastasis, and suppressing adaptive immunity. They can have a dual effect on cancer therapies, either hindering antitumor activity by promoting tissue repair or enhancing it through antitumor functions. TAMs express checkpoint molecules like PD-L1, making them targets for immunotherapy. Therapeutic strategies targeting TAMs include blocking their recruitment and survival, reeducating them to an antitumor M1-like state, and using monoclonal antibodies to kill cancer cells. TAMs can also be used to tailor therapies and complement chemotherapy and immunotherapy. TAMs originate from blood monocytes and tissue-resident macrophages, with their function influenced by factors like hypoxia and cytokines. They contribute to tumor progression by promoting angiogenesis, tissue remodeling, and immunosuppression. TAMs can be prognostic biomarkers, with high infiltration associated with worse outcomes in some cancers but better outcomes in others, depending on the context and treatment. TAMs can also predict response to chemotherapy and immunotherapy. Chemotherapy and radiotherapy can be influenced by TAMs, with TAMs either enhancing or reducing the effectiveness of these treatments. TAMs can also affect the response to checkpoint inhibitors by expressing checkpoint molecules. Anti-angiogenic therapies targeting VEGF and angiopoietin-2 can be complemented by TAM-targeting strategies. TAMs can be targeted through inhibitors of CSF-1R, which reduces TAM infiltration and improves treatment outcomes. Macrophage-targeting strategies include blocking recruitment, survival, and polarization. Anti-chemokine therapies, CSF-1R inhibitors, and targeting the CD47/SIRP-α pathway are promising approaches. TAMs can also be targeted through checkpoint inhibitors and by modulating their function to enhance antitumor immunity. These strategies are being evaluated in clinical trials and show potential for improving cancer treatment outcomes.Tumor-associated macrophages (TAMs) play a critical role in tumor progression by promoting genetic instability, nurturing cancer stem cells, facilitating metastasis, and suppressing adaptive immunity. They can have a dual effect on cancer therapies, either hindering antitumor activity by promoting tissue repair or enhancing it through antitumor functions. TAMs express checkpoint molecules like PD-L1, making them targets for immunotherapy. Therapeutic strategies targeting TAMs include blocking their recruitment and survival, reeducating them to an antitumor M1-like state, and using monoclonal antibodies to kill cancer cells. TAMs can also be used to tailor therapies and complement chemotherapy and immunotherapy. TAMs originate from blood monocytes and tissue-resident macrophages, with their function influenced by factors like hypoxia and cytokines. They contribute to tumor progression by promoting angiogenesis, tissue remodeling, and immunosuppression. TAMs can be prognostic biomarkers, with high infiltration associated with worse outcomes in some cancers but better outcomes in others, depending on the context and treatment. TAMs can also predict response to chemotherapy and immunotherapy. Chemotherapy and radiotherapy can be influenced by TAMs, with TAMs either enhancing or reducing the effectiveness of these treatments. TAMs can also affect the response to checkpoint inhibitors by expressing checkpoint molecules. Anti-angiogenic therapies targeting VEGF and angiopoietin-2 can be complemented by TAM-targeting strategies. TAMs can be targeted through inhibitors of CSF-1R, which reduces TAM infiltration and improves treatment outcomes. Macrophage-targeting strategies include blocking recruitment, survival, and polarization. Anti-chemokine therapies, CSF-1R inhibitors, and targeting the CD47/SIRP-α pathway are promising approaches. TAMs can also be targeted through checkpoint inhibitors and by modulating their function to enhance antitumor immunity. These strategies are being evaluated in clinical trials and show potential for improving cancer treatment outcomes.