BACKGROUND: Colorectal cancer (CRC) remains a major global health burden due to its high incidence and mortality, with treatment efficacy often hindered by tumor heterogeneity, drug resistance, and a complex tumor microenvironment (TME). Lactate metabolism plays a pivotal role in reshaping the TME, promoting immune evasion and epithelial-mesenchymal transition, making it a promising target for novel therapeutic strategies and prognostic modeling in CRC. AIM: To offer an in-depth analysis of the role of lactate metabolism in CRC, highlighting its significance in the TME and therapeutic response. METHODS: Utilizing single-cell and transcriptomic data from the Gene Expression Omnibus and The Cancer Genome Atlas, we identified key lactate metabolic activities, particularly in the monocyte/macrophage subpopulation. RESULTS: Seven lactate metabolism-associated genes were significantly linked to CRC prognosis and used to construct a predictive model. This model accurately forecasts patient outcomes and reveals notable distinct patterns of immune infiltration and transcriptomic profiles mutation profiles between high- and low-risk groups. High-risk patients demonstrated elevated immune cell infiltration, increased mutation frequencies, and heightened sensitivity to specific drugs (AZD6482, tozasertib, and SB216763), providing a foundation for personalized treatment approaches. Additionally, a nomogram integrating clinical and metabolic data effectively predicted 1-, 3-, and 5-year survival rates. CONCLUSION: This report underscored the pivotal mechanism of lactate metabolism in CRC prognosis and suggest novel avenues for therapeutic intervention.