Lactate, once considered a waste product, has emerged as a critical regulator in cancer development, maintenance, and metastasis. Tumor cells metabolize lactate as an energy source and shuttle it to neighboring cells, stroma, and vascular endothelial cells, inducing metabolic reprogramming. Lactate also promotes tumor inflammation and angiogenesis. The Warburg effect, where cancer cells rely on aerobic glycolysis to support proliferation, is driven by oncogenic lesions that induce the expression of glycolytic enzymes. Glutamine catabolism supports anabolic growth and redox homeostasis. Monocarboxylate transporters (MCTs) are essential for lactate transport and pH regulation. Lactate dehydrogenase (LDHA) mediates the conversion of pyruvate to lactate and is an emerging target for cancer therapy. LDHA inhibitors, such as gossypol and galloflavin, show promise in inhibiting cancer growth. MCT1 and MCT4 are highly expressed in several cancers and are potential therapeutic targets. Targeting MCT chaperones, such as CD147, may also be effective. Understanding lactate shuttling in human malignancies is crucial for optimizing therapeutic strategies.Lactate, once considered a waste product, has emerged as a critical regulator in cancer development, maintenance, and metastasis. Tumor cells metabolize lactate as an energy source and shuttle it to neighboring cells, stroma, and vascular endothelial cells, inducing metabolic reprogramming. Lactate also promotes tumor inflammation and angiogenesis. The Warburg effect, where cancer cells rely on aerobic glycolysis to support proliferation, is driven by oncogenic lesions that induce the expression of glycolytic enzymes. Glutamine catabolism supports anabolic growth and redox homeostasis. Monocarboxylate transporters (MCTs) are essential for lactate transport and pH regulation. Lactate dehydrogenase (LDHA) mediates the conversion of pyruvate to lactate and is an emerging target for cancer therapy. LDHA inhibitors, such as gossypol and galloflavin, show promise in inhibiting cancer growth. MCT1 and MCT4 are highly expressed in several cancers and are potential therapeutic targets. Targeting MCT chaperones, such as CD147, may also be effective. Understanding lactate shuttling in human malignancies is crucial for optimizing therapeutic strategies.