Abstract: Against the era backdrop of precision medicine, the diagnostic and therapeutic paradigm for colorectal cancer is shifting from empiric treatment to molecularly driven strategies. The application of molecular subtyping, liquid biopsy, and artificial intelligence has significantly enhanced the precision of colorectal cancer screening, diagnosis, and treatment. The authors systema-tically review advances and challenges in precision screening, molecular profiling, targeted and immunotherapies, and perioperative management, and envision the prospects for multi-omics inte-gration and artificial intelligence in achieving end-to-end precision management, with the aim of informing clinical practice and scientific research.