This review explores the role of macrophage metabolism in cancer immunotherapy. Macrophages, particularly tumor-associated macrophages (TAMs), play a critical role in tumor progression and immune suppression. The metabolic state of TAMs influences tumor growth and antitumor immune responses. Current classifications of macrophage phenotypes, such as M1 (inflammatory) and M2 (immunosuppressive), are oversimplified, as TAMs exist in a continuous spectrum of metabolic states. Understanding these nuances is essential for developing effective metabolic interventions. TAMs contribute to tumor progression through mechanisms such as immune suppression, angiogenesis, and resistance to chemotherapy. Their metabolic programming, including aerobic glycolysis and mitochondrial metabolism, is crucial for their function. Inflammatory macrophages exhibit a "broken" TCA cycle, allowing intermediates to support inflammatory responses. Conversely, immunosuppressive TAMs rely on glucose metabolism to support TCA cycle function. Targeting these metabolic pathways can enhance antitumor immunity. The pentose phosphate pathway supports inflammatory myeloid activation by providing NADPH, which is essential for maintaining glutathione levels and protecting cells from oxidative stress. Fatty acid oxidation (FAO) is another critical metabolic pathway in TAMs, but its role in immunosuppression is complex and context-dependent. Targeting FAO may not be as essential as previously thought. Metabolic inhibitors such as 2-deoxyglucose (2-DG) and metformin can reprogram TAMs to promote antitumor immunity. However, these compounds have off-target effects that must be carefully considered. Targeting arginine metabolism, such as with inhibitors of arginase 1 (Arg1), can enhance immunotherapy by reducing immunosuppression. Similarly, glutamine metabolism is critical for TAM function and tumor growth, and inhibitors of glutaminase 1 (GLS1) can disrupt both TAMs and tumor cells. Arginine metabolism is central to myeloid function in tumors, with arginine being a key substrate for polyamine synthesis and NO production. Inhibiting polyamine synthesis can enhance T cell infiltration and immunotherapy. Targeting iNOS-mediated immunosuppression can also promote antitumor responses. Glutamine metabolism is essential for macrophage activation and polarization, with glutamine-derived α-ketoglutarate (α-KG) playing a key role in immunosuppressive macrophage function. Inhibitors of glutaminase 1 (GLS1) can disrupt both TAMs and tumor cells. Overall, metabolic reprogramming of TAMs offers a promising strategy for enhancing antitumor immunity. However, challenges remain in developing specific and effective metabolic therapies, particularly for brain tumors due to the blood-brain barrier. Future research should focus on refining drug specificity and delivery methods to maximize therapeutic efficacy.This review explores the role of macrophage metabolism in cancer immunotherapy. Macrophages, particularly tumor-associated macrophages (TAMs), play a critical role in tumor progression and immune suppression. The metabolic state of TAMs influences tumor growth and antitumor immune responses. Current classifications of macrophage phenotypes, such as M1 (inflammatory) and M2 (immunosuppressive), are oversimplified, as TAMs exist in a continuous spectrum of metabolic states. Understanding these nuances is essential for developing effective metabolic interventions. TAMs contribute to tumor progression through mechanisms such as immune suppression, angiogenesis, and resistance to chemotherapy. Their metabolic programming, including aerobic glycolysis and mitochondrial metabolism, is crucial for their function. Inflammatory macrophages exhibit a "broken" TCA cycle, allowing intermediates to support inflammatory responses. Conversely, immunosuppressive TAMs rely on glucose metabolism to support TCA cycle function. Targeting these metabolic pathways can enhance antitumor immunity. The pentose phosphate pathway supports inflammatory myeloid activation by providing NADPH, which is essential for maintaining glutathione levels and protecting cells from oxidative stress. Fatty acid oxidation (FAO) is another critical metabolic pathway in TAMs, but its role in immunosuppression is complex and context-dependent. Targeting FAO may not be as essential as previously thought. Metabolic inhibitors such as 2-deoxyglucose (2-DG) and metformin can reprogram TAMs to promote antitumor immunity. However, these compounds have off-target effects that must be carefully considered. Targeting arginine metabolism, such as with inhibitors of arginase 1 (Arg1), can enhance immunotherapy by reducing immunosuppression. Similarly, glutamine metabolism is critical for TAM function and tumor growth, and inhibitors of glutaminase 1 (GLS1) can disrupt both TAMs and tumor cells. Arginine metabolism is central to myeloid function in tumors, with arginine being a key substrate for polyamine synthesis and NO production. Inhibiting polyamine synthesis can enhance T cell infiltration and immunotherapy. Targeting iNOS-mediated immunosuppression can also promote antitumor responses. Glutamine metabolism is essential for macrophage activation and polarization, with glutamine-derived α-ketoglutarate (α-KG) playing a key role in immunosuppressive macrophage function. Inhibitors of glutaminase 1 (GLS1) can disrupt both TAMs and tumor cells. Overall, metabolic reprogramming of TAMs offers a promising strategy for enhancing antitumor immunity. However, challenges remain in developing specific and effective metabolic therapies, particularly for brain tumors due to the blood-brain barrier. Future research should focus on refining drug specificity and delivery methods to maximize therapeutic efficacy.