The tumor microenvironment is a complex ecosystem that evolves with and supports tumor cells during their transition to malignancy. Macrophages, a key component of this environment, are abundant and present at all stages of tumor progression. They play a pro-tumoral role, stimulating angiogenesis, enhancing tumor cell invasion, motility, and intravasation, and promoting metastasis. Macrophages also act as immunosuppressors, preventing tumor cell attack by natural killer and T cells. Therapeutic approaches targeting these pro-tumoral roles have shown promise in pre-clinical models and early clinical trials, suggesting that macrophages are attractive targets for combination therapies in cancer treatment. The origins of tumor-associated macrophages (TAMs) are still under investigation, but evidence suggests they arise from both yolk sac progenitors and circulating monocytes. TAMs express various receptors, cytokines, chemokines, and enzymes that contribute to their immunosuppressive functions. Targeting TAMs or specific sub-populations, such as TIE2+ or metastasis-associated macrophages (MAMs), may be a promising strategy for cancer therapy. Recent studies have shown that inhibiting CSF1 signaling can reduce tumor progression and metastasis, and this approach has shown clinical efficacy. Further research is needed to define the diverse origins and functions of macrophages in different cancers to develop more sophisticated and targeted therapies.The tumor microenvironment is a complex ecosystem that evolves with and supports tumor cells during their transition to malignancy. Macrophages, a key component of this environment, are abundant and present at all stages of tumor progression. They play a pro-tumoral role, stimulating angiogenesis, enhancing tumor cell invasion, motility, and intravasation, and promoting metastasis. Macrophages also act as immunosuppressors, preventing tumor cell attack by natural killer and T cells. Therapeutic approaches targeting these pro-tumoral roles have shown promise in pre-clinical models and early clinical trials, suggesting that macrophages are attractive targets for combination therapies in cancer treatment. The origins of tumor-associated macrophages (TAMs) are still under investigation, but evidence suggests they arise from both yolk sac progenitors and circulating monocytes. TAMs express various receptors, cytokines, chemokines, and enzymes that contribute to their immunosuppressive functions. Targeting TAMs or specific sub-populations, such as TIE2+ or metastasis-associated macrophages (MAMs), may be a promising strategy for cancer therapy. Recent studies have shown that inhibiting CSF1 signaling can reduce tumor progression and metastasis, and this approach has shown clinical efficacy. Further research is needed to define the diverse origins and functions of macrophages in different cancers to develop more sophisticated and targeted therapies.