The article reviews the role of lactate and lactylation in malignancy and its potential in immunotherapy. Lactate, produced by cancer cells through glycolysis, plays a crucial role in maintaining an acidic tumor microenvironment (TME), which suppresses immune responses and promotes tumor progression. Lactylation, a post-translational modification involving the attachment of lactic acid to protein lysine residues, influences gene expression and modulates immune cell function. The review highlights how lactate and lactylation affect tumor cells and immune cells, including the activation of regulatory T cells (Tregs) and natural killer (NK) cells, and the transformation of tumor-associated macrophages (TAMs) into an M2-like phenotype. Recent studies have explored the therapeutic potential of targeting lactate and lactylation in combination with immune checkpoint inhibitors (ICIs) and other immunotherapies, such as CAR-T therapy. The article discusses the challenges and limitations of these approaches, including the risk of side effects and the need for more specific inhibitors. Overall, the review underscores the importance of understanding the complex interplay between lactate, lactylation, and the immune system in cancer, and suggests that targeting these processes could be a promising strategy for improving cancer treatment outcomes.The article reviews the role of lactate and lactylation in malignancy and its potential in immunotherapy. Lactate, produced by cancer cells through glycolysis, plays a crucial role in maintaining an acidic tumor microenvironment (TME), which suppresses immune responses and promotes tumor progression. Lactylation, a post-translational modification involving the attachment of lactic acid to protein lysine residues, influences gene expression and modulates immune cell function. The review highlights how lactate and lactylation affect tumor cells and immune cells, including the activation of regulatory T cells (Tregs) and natural killer (NK) cells, and the transformation of tumor-associated macrophages (TAMs) into an M2-like phenotype. Recent studies have explored the therapeutic potential of targeting lactate and lactylation in combination with immune checkpoint inhibitors (ICIs) and other immunotherapies, such as CAR-T therapy. The article discusses the challenges and limitations of these approaches, including the risk of side effects and the need for more specific inhibitors. Overall, the review underscores the importance of understanding the complex interplay between lactate, lactylation, and the immune system in cancer, and suggests that targeting these processes could be a promising strategy for improving cancer treatment outcomes.