Fatty acid metabolism in immune cells is a critical target for tumor immunotherapy. The competition for nutrients between tumor cells and immune cells in the tumor microenvironment (TME) significantly influences immune cell function and tumor progression. Tumor cells reprogram their metabolism to survive in hypoxic and acidic environments, while immune cells rely on fatty acid metabolism for energy, signaling, and function. Dysregulation of fatty acid metabolism in the TME affects immune cell activation, differentiation, and tumor immune escape. Recent studies highlight the potential of targeting fatty acid metabolism in immune cells to enhance anti-tumor immunity. Immune cells, including CD8+ T cells, regulatory T cells (Tregs), and macrophages, have distinct fatty acid metabolic profiles. CD8+ T cells depend on fatty acid oxidation for energy and function, while Tregs use glycolysis and fatty acid oxidation to maintain immunosuppressive activity. Macrophages, particularly M2 macrophages, rely on fatty acid oxidation for energy and immunosuppressive functions. Dysregulation of fatty acid metabolism in these cells can impair immune responses and promote tumor growth. Fatty acid metabolism is closely linked to immune checkpoint pathways, such as PD-1/PD-L1. Targeting fatty acid metabolism in immune cells can enhance the efficacy of immune checkpoint inhibitors. For example, PPARα agonists like fenofibrate improve CD8+ T cell function and synergize with PD-1 blockers. Similarly, PPARγ coactivator 1α (PGC-1α) enhances fatty acid oxidation and supports T cell survival. Fatty acid metabolism also plays a role in dendritic cell (DC) function, which is crucial for antigen presentation and T cell activation. Dysregulation of fatty acid metabolism in DCs can impair immune responses and promote tumor immune escape. Enhancing fatty acid metabolism in DCs may improve anti-tumor immunity. Combining fatty acid metabolism-targeting therapies with immunotherapy, such as adoptive cell therapy and cancer vaccines, shows promise. For example, PPARα agonists combined with cancer vaccines delay tumor progression in mouse models. Short-chain fatty acids (SCFAs) like valerate and butyrate enhance the efficacy of CAR-T cells and CTLs by increasing effector cytokine production. Overall, targeting fatty acid metabolism in immune cells offers new strategies for improving tumor immunotherapy. Understanding the metabolic adaptations of immune cells in the TME is essential for developing effective therapies. Future research should focus on the interplay between fatty acid metabolism and immune cell function to enhance anti-tumor immunity.Fatty acid metabolism in immune cells is a critical target for tumor immunotherapy. The competition for nutrients between tumor cells and immune cells in the tumor microenvironment (TME) significantly influences immune cell function and tumor progression. Tumor cells reprogram their metabolism to survive in hypoxic and acidic environments, while immune cells rely on fatty acid metabolism for energy, signaling, and function. Dysregulation of fatty acid metabolism in the TME affects immune cell activation, differentiation, and tumor immune escape. Recent studies highlight the potential of targeting fatty acid metabolism in immune cells to enhance anti-tumor immunity. Immune cells, including CD8+ T cells, regulatory T cells (Tregs), and macrophages, have distinct fatty acid metabolic profiles. CD8+ T cells depend on fatty acid oxidation for energy and function, while Tregs use glycolysis and fatty acid oxidation to maintain immunosuppressive activity. Macrophages, particularly M2 macrophages, rely on fatty acid oxidation for energy and immunosuppressive functions. Dysregulation of fatty acid metabolism in these cells can impair immune responses and promote tumor growth. Fatty acid metabolism is closely linked to immune checkpoint pathways, such as PD-1/PD-L1. Targeting fatty acid metabolism in immune cells can enhance the efficacy of immune checkpoint inhibitors. For example, PPARα agonists like fenofibrate improve CD8+ T cell function and synergize with PD-1 blockers. Similarly, PPARγ coactivator 1α (PGC-1α) enhances fatty acid oxidation and supports T cell survival. Fatty acid metabolism also plays a role in dendritic cell (DC) function, which is crucial for antigen presentation and T cell activation. Dysregulation of fatty acid metabolism in DCs can impair immune responses and promote tumor immune escape. Enhancing fatty acid metabolism in DCs may improve anti-tumor immunity. Combining fatty acid metabolism-targeting therapies with immunotherapy, such as adoptive cell therapy and cancer vaccines, shows promise. For example, PPARα agonists combined with cancer vaccines delay tumor progression in mouse models. Short-chain fatty acids (SCFAs) like valerate and butyrate enhance the efficacy of CAR-T cells and CTLs by increasing effector cytokine production. Overall, targeting fatty acid metabolism in immune cells offers new strategies for improving tumor immunotherapy. Understanding the metabolic adaptations of immune cells in the TME is essential for developing effective therapies. Future research should focus on the interplay between fatty acid metabolism and immune cell function to enhance anti-tumor immunity.