This review explores the role of lactate-lactylation in malignancy and its potential in immunotherapy. Lactate, a byproduct of glycolysis, has been shown to contribute to tumor growth, migration, and invasion. Post-translational lactylation of proteins, particularly histones and non-histones, plays a critical role in regulating gene expression and is increasingly recognized as a key factor in cancer progression. The tumor microenvironment (TME) is influenced by lactate, which can suppress anti-tumor immune responses by altering the function of immune cells such as T cells, NK cells, and regulatory T cells. Lactate also promotes tumor angiogenesis, metastasis, and immune evasion. Lactylation is a post-translational modification that involves the covalent attachment of lactic acid to lysine residues in proteins. It has been implicated in various cancers, including ocular melanoma, colorectal cancer, gastric cancer, and others. Lactylation can influence tumor cell metabolism, immune cell function, and the tumor microenvironment. Targeting lactate-lactylation in tumor immunotherapy is a promising approach to enhance immune responses and improve cancer treatment outcomes. Studies have shown that lactate can enhance the effectiveness of immunotherapies such as checkpoint inhibitors and CAR-T therapy. Inhibiting lactate transporters like MCT4 and targeting lactate metabolism can improve the efficacy of anti-PD-1 and anti-PD-L1 therapies. Additionally, lactate can enhance the immunogenicity of tumor vaccines by promoting dendritic cell maturation and increasing T cell infiltration. The review also discusses the challenges and limitations of targeting lactate-lactylation in cancer therapy, including potential side effects and the need for more specific inhibitors. Overall, lactate-lactylation represents a promising area of research for developing novel therapeutic strategies in cancer treatment.This review explores the role of lactate-lactylation in malignancy and its potential in immunotherapy. Lactate, a byproduct of glycolysis, has been shown to contribute to tumor growth, migration, and invasion. Post-translational lactylation of proteins, particularly histones and non-histones, plays a critical role in regulating gene expression and is increasingly recognized as a key factor in cancer progression. The tumor microenvironment (TME) is influenced by lactate, which can suppress anti-tumor immune responses by altering the function of immune cells such as T cells, NK cells, and regulatory T cells. Lactate also promotes tumor angiogenesis, metastasis, and immune evasion. Lactylation is a post-translational modification that involves the covalent attachment of lactic acid to lysine residues in proteins. It has been implicated in various cancers, including ocular melanoma, colorectal cancer, gastric cancer, and others. Lactylation can influence tumor cell metabolism, immune cell function, and the tumor microenvironment. Targeting lactate-lactylation in tumor immunotherapy is a promising approach to enhance immune responses and improve cancer treatment outcomes. Studies have shown that lactate can enhance the effectiveness of immunotherapies such as checkpoint inhibitors and CAR-T therapy. Inhibiting lactate transporters like MCT4 and targeting lactate metabolism can improve the efficacy of anti-PD-1 and anti-PD-L1 therapies. Additionally, lactate can enhance the immunogenicity of tumor vaccines by promoting dendritic cell maturation and increasing T cell infiltration. The review also discusses the challenges and limitations of targeting lactate-lactylation in cancer therapy, including potential side effects and the need for more specific inhibitors. Overall, lactate-lactylation represents a promising area of research for developing novel therapeutic strategies in cancer treatment.