Abstract: Colorectal cancer (CRC) ranks among the most prevalent malignancies globally, posing a substantial threat to public health. At initial diagnosis, 20%-25% of patients present with metastatic disease, while 50% of localized cases eventually progress to metastatic colorectal cancer (mCRC). The prognosis for mCRC remains poor, with a 5-year survival rate below 20%. Precision medicine, an individualized and deeply stratified approach to disease prevention and management, demonstrates exceptional potential in treatment of CRC.The pathogenesis and progression of CRC are closely linked to diverse genetic abnormalities. Through genomic profiling to define clinically actionable subgroups, the efficacy of targeted therapies and immunotherapies can be significantly enhanced. The mutational status of RAS and BRAF genes holds critical importance in guiding therapeutic selection for targeted agents. Patients with DNA mismatch repair deficiency/microsatellite instability-high status exhibit notable responses to immunotherapies. Emerging modalities such as chimeric antigen receptor-T-cell immunotherapy and fecal microbiota transplantation show therapeutic promise in mCRC. Additionally, circulating tumor DNA, multi-omics technologies, and artificial intelligence are increasingly utilized in early screening, diagnostic refinement, treatment response monitoring, and prognostic prediction. The authors comprehensively discuss the current status and advances in precision diagnosis and treatment of metastatic colorectal cancer from perspectives including genomic abnormalities, targeted therapy, immunotherapy, and future directions.