Background <p>Multimodal rehabilitation programs represented comprehensive preoperative intervention strategies designed to optimize patients’ physical, nutritional, and psychological status. These programs have shown potential benefits in enhancing recovery, improving quality of life, and optimizing functional outcomes across various clinical contexts.</p> Objective <p>This review aimed to evaluate the feasibility and clinical effectiveness of home-based multimodal prehabilitation for patients undergoing colorectal cancer surgery.</p> Methods <p>A systematic review and meta-analysis were conducted using RevMan 5.4. The primary outcome was the change in the 6-min walk test (6MWT) during the preoperative period. Secondary outcomes included 30-day postoperative complications, emergency department visits, hospital readmission, and mental health outcomes measured using the Hospital Anxiety and Depression Scale (HADS).</p> Results <p>Prehabilitation significantly improved the preoperative 6MWT [MD = 40.61, 95% CI (6.23, 74.99), <i>P</i> = 0.02]. However, no significant improvement was observed at 4–6&#xa0;weeks [MD = 49.67, 95% CI (–35.50, 134.84), <i>P</i> = 0.25] or 8&#xa0;weeks postoperatively [MD = 26.58, 95% CI (–8.88, 62.04), <i>P</i> = 0.14]. Prehabilitation did not significantly affect total hospitalization, 30-day postoperative complications, emergency department visits, or readmission rates. Additionally, no significant improvements were found in HADS-anxiety or HADS-depression scores at 8&#xa0;weeks.</p> Conclusions <p>Home-based multimodal prehabilitation significantly improved physical function before colorectal cancer surgery; however, these benefits were not sustained postoperatively. More intensive or prolonged programs, combined with postoperative rehabilitation, may be necessary to maintain preoperative gains. Larger trials with extended follow-up periods are needed to confirm long-term clinical effects.</p> Trial Registration <p>The study protocol was registered in PROSPERO (CRD42023439715).</p>