Macrophages play a critical role in tumor immunity and immunotherapy. They are involved in promoting proliferation, angiogenesis, and metastasis, and their suppressive capacity is driven by microenvironmental cues such as hypoxia and fibrosis. Tumor-associated macrophages (TAMs) are associated with poor prognosis in solid tumors and suppress responses to standard therapies. Combinatorial approaches, including checkpoint blockade, are showing promise in clinical trials. The diversity of macrophage functions is regulated by developmental origin, tissue of residence, and microenvironmental cues. Embryonic-derived TAMs have distinct phenotypes and functions compared to monocyte-derived TAMs. Metabolic factors, such as hypoxia and glucose availability, and fibrotic stroma, can significantly impact macrophage function and tumor growth. Macrophages can directly or indirectly suppress T cell responses, and their recruitment and survival can be targeted therapeutically. Reprogramming TAMs towards an anti-tumor phenotype is another strategy, with CD40 agonists showing promising results. Future directions include understanding the optimal therapeutic approaches and combining these with immunotherapies to improve outcomes for cancer patients.Macrophages play a critical role in tumor immunity and immunotherapy. They are involved in promoting proliferation, angiogenesis, and metastasis, and their suppressive capacity is driven by microenvironmental cues such as hypoxia and fibrosis. Tumor-associated macrophages (TAMs) are associated with poor prognosis in solid tumors and suppress responses to standard therapies. Combinatorial approaches, including checkpoint blockade, are showing promise in clinical trials. The diversity of macrophage functions is regulated by developmental origin, tissue of residence, and microenvironmental cues. Embryonic-derived TAMs have distinct phenotypes and functions compared to monocyte-derived TAMs. Metabolic factors, such as hypoxia and glucose availability, and fibrotic stroma, can significantly impact macrophage function and tumor growth. Macrophages can directly or indirectly suppress T cell responses, and their recruitment and survival can be targeted therapeutically. Reprogramming TAMs towards an anti-tumor phenotype is another strategy, with CD40 agonists showing promising results. Future directions include understanding the optimal therapeutic approaches and combining these with immunotherapies to improve outcomes for cancer patients.