Lactate, once considered a waste product of glycolysis, has emerged as a critical regulator of cancer development, maintenance, and metastasis. Tumor lactate levels correlate with increased metastasis, tumor recurrence, and poor outcomes. Lactate mediates cancer cell intrinsic effects on metabolism and has non-tumor cell autonomous effects that drive tumorigenesis. Tumor cells can metabolize lactate as an energy source and shuttle lactate to neighboring cancer cells, adjacent stroma, and vascular endothelial cells, inducing metabolic reprogramming. Lactate also promotes tumor inflammation and functions as a signaling molecule that stimulates tumor angiogenesis. Targeting lactate metabolism is a promising approach for cancer therapeutics. Cancer cells rely on aerobic glycolysis, a process known as the Warburg effect, to support proliferation and anabolic growth. This process generates ATP and diverts carbon from glucose into precursors for nucleotides, proteins, and lipids. Glutamine catabolism also supports anabolic growth, sustains TCA cycle intermediates, and regulates redox homeostasis. These activities augment lactate production. Oncogenic lesions drive the switch to aerobic glycolysis and lactate production by inducing the expression and activation of glycolytic enzymes. Key regulators include PI3K/AKT signaling, MYC, and HIF-1α. These factors regulate the expression of glycolytic enzymes and glutamine catabolism, which contribute to lactate production. Lactate homeostasis in cancer cells requires its transport by monocarboxylate transporters (MCTs), which facilitate the influx and efflux of lactate across the plasma membrane. MCTs are critical regulators of intracellular lactate and pH. MCT1 and MCT4 are highly expressed in several malignancies and are associated with poor prognosis. Targeting MCTs is an attractive strategy for cancer therapeutics. MCTs are also necessary for lactate import into cells that use lactate as an oxidative metabolite or for gluconeogenesis. Lactate dehydrogenase (LDH) mediates the bidirectional conversion of pyruvate and lactate and is an emerging anticancer target. LDHA is a key isoform in many tumors and is associated with poor prognosis. Inhibitors of LDHA, such as FX11 and gossypol, have shown antitumor activity in xenograft models. However, the efficacy of LDHA inhibitors may vary by cancer type and metabolic phenotype. Targeting MCT chaperones, such as CD147, is also an attractive strategy. CD147 is required for the surface expression of MCTs and is ubiquitously expressed. Anti-CD147 antibodies can induce antibody-dependent cell-mediated cytotoxicity and deliver drug payloads to CD147/MCT-expressing tumor cells. The lactate shuttle facilitates theLactate, once considered a waste product of glycolysis, has emerged as a critical regulator of cancer development, maintenance, and metastasis. Tumor lactate levels correlate with increased metastasis, tumor recurrence, and poor outcomes. Lactate mediates cancer cell intrinsic effects on metabolism and has non-tumor cell autonomous effects that drive tumorigenesis. Tumor cells can metabolize lactate as an energy source and shuttle lactate to neighboring cancer cells, adjacent stroma, and vascular endothelial cells, inducing metabolic reprogramming. Lactate also promotes tumor inflammation and functions as a signaling molecule that stimulates tumor angiogenesis. Targeting lactate metabolism is a promising approach for cancer therapeutics. Cancer cells rely on aerobic glycolysis, a process known as the Warburg effect, to support proliferation and anabolic growth. This process generates ATP and diverts carbon from glucose into precursors for nucleotides, proteins, and lipids. Glutamine catabolism also supports anabolic growth, sustains TCA cycle intermediates, and regulates redox homeostasis. These activities augment lactate production. Oncogenic lesions drive the switch to aerobic glycolysis and lactate production by inducing the expression and activation of glycolytic enzymes. Key regulators include PI3K/AKT signaling, MYC, and HIF-1α. These factors regulate the expression of glycolytic enzymes and glutamine catabolism, which contribute to lactate production. Lactate homeostasis in cancer cells requires its transport by monocarboxylate transporters (MCTs), which facilitate the influx and efflux of lactate across the plasma membrane. MCTs are critical regulators of intracellular lactate and pH. MCT1 and MCT4 are highly expressed in several malignancies and are associated with poor prognosis. Targeting MCTs is an attractive strategy for cancer therapeutics. MCTs are also necessary for lactate import into cells that use lactate as an oxidative metabolite or for gluconeogenesis. Lactate dehydrogenase (LDH) mediates the bidirectional conversion of pyruvate and lactate and is an emerging anticancer target. LDHA is a key isoform in many tumors and is associated with poor prognosis. Inhibitors of LDHA, such as FX11 and gossypol, have shown antitumor activity in xenograft models. However, the efficacy of LDHA inhibitors may vary by cancer type and metabolic phenotype. Targeting MCT chaperones, such as CD147, is also an attractive strategy. CD147 is required for the surface expression of MCTs and is ubiquitously expressed. Anti-CD147 antibodies can induce antibody-dependent cell-mediated cytotoxicity and deliver drug payloads to CD147/MCT-expressing tumor cells. The lactate shuttle facilitates the