Tumor-associated macrophages (TAMs) play a critical role in tumor metastasis by creating an immunosuppressive tumor microenvironment (TME) through the production of cytokines, chemokines, and growth factors. They facilitate the metastatic cascade by promoting tumor cell invasion, vascularization, intravasation, extravasation, and survival in circulation. TAMs also support the formation of pre-metastatic niches, which are essential for tumor cell colonization in distant sites. TAMs are primarily derived from blood monocytes and tissue-resident macrophages, and their polarization into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes is regulated by various signals, including cytokines, growth factors, and epigenetic regulators. M2-like TAMs are particularly associated with tumor progression and metastasis. TAMs contribute to metastasis by promoting angiogenesis, ECM degradation, and tumor cell survival. Therapeutic strategies targeting TAMs, such as inhibiting their survival, suppressing M2 polarization, or blocking their recruitment, are being explored as potential treatments for cancer. Agents like trabectedin and lurbinectedin have shown promise in targeting TAMs, while CD40 agonists and CSF-1 inhibitors are also under investigation. Despite these advances, challenges remain in translating TAM-targeting therapies into clinical success due to the complexity of TAM biology and the heterogeneity of TAM responses. Further research is needed to better understand TAM functions and develop effective, targeted therapies for cancer.Tumor-associated macrophages (TAMs) play a critical role in tumor metastasis by creating an immunosuppressive tumor microenvironment (TME) through the production of cytokines, chemokines, and growth factors. They facilitate the metastatic cascade by promoting tumor cell invasion, vascularization, intravasation, extravasation, and survival in circulation. TAMs also support the formation of pre-metastatic niches, which are essential for tumor cell colonization in distant sites. TAMs are primarily derived from blood monocytes and tissue-resident macrophages, and their polarization into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes is regulated by various signals, including cytokines, growth factors, and epigenetic regulators. M2-like TAMs are particularly associated with tumor progression and metastasis. TAMs contribute to metastasis by promoting angiogenesis, ECM degradation, and tumor cell survival. Therapeutic strategies targeting TAMs, such as inhibiting their survival, suppressing M2 polarization, or blocking their recruitment, are being explored as potential treatments for cancer. Agents like trabectedin and lurbinectedin have shown promise in targeting TAMs, while CD40 agonists and CSF-1 inhibitors are also under investigation. Despite these advances, challenges remain in translating TAM-targeting therapies into clinical success due to the complexity of TAM biology and the heterogeneity of TAM responses. Further research is needed to better understand TAM functions and develop effective, targeted therapies for cancer.