As the global incidence of colorectal cancer (CRC) continues to rise, particularly among young adults, the integration of precision medicine into clinical management represents an evolving priority. However, the clinical maturity and evidence base of precision oncology differ substantially between metastatic and curative-intent settings. In metastatic CRC, actionable biomarkers frequently direct therapy selection and sequencing, with several matched regimens now incorporated into routine practice. In contrast, curative-intent precision strategies must meet a higher evidentiary bar because many patients are cured by surgery and conventional adjuvant therapy alone. Consequently, any therapeutic escalation requires a clear survival benefit without imposing unnecessary toxicity. This mini review focuses on clinical positioning: what is guideline-positioned today, what is supported by emerging prospective evidence, and what remains investigational. In curative-intent disease, we highlight postoperative circulating tumor DNA (ctDNA) as a powerful prognostic tool for molecular residual disease risk stratification, while emphasizing that routine ctDNA-guided treatment or surveillance modifications remain unproven outside of prospective interventional trials. We also summarize emerging, trial-defined approaches evaluating neoadjuvant and adjuvant immunotherapy in biologically selected early-stage subsets. In metastatic CRC, we review the major actionable subgroups and their matched therapies and discuss practical implementation barriers that affect real-world delivery, including tissue adequacy, turnaround time, acquired resistance, and equitable access. Overall, precision oncology is most practice-defining in metastatic CRC, whereas broader adoption in curative-intent disease still depends on prospective validation showing that biomarker-guided decisions improve disease-free and overall survival.