This study investigates the safety and efficacy of a multimodal approach, integrating radiotherapy, chemotherapy, and surgery for the management of cancer patients. This review systematically reviewed English-language literature from digital repositories, namely Web of Science, Scopus, Google Scholar, PubMed, and the Cochrane Library. The search strategy employed a targeted selection of keywords: "chemotherapy," "radiotherapy," "multimodal," and "surgery," encompassing publications published before January 2024. This comprehensive approach was designed to encapsulate the breadth of existing research on the integration of these therapeutic modalities in cancer treatment, ensuring a robust analysis of their collective efficacy and safety. While existing literature has examined the efficacy and safety of the multimodal approach in various cancer types, each study typically focuses on a single type, such as breast, brain, or bladder cancer. This review is distinguished by its evaluation of the approach's efficacy across different cancer types, including but not limited to breast, bladder, esophageal, salivary gland, and cervical cancers. The integration of chemotherapy, surgery, and radiotherapy emerges as the optimal strategy for cancer management, irrespective of cancer type or location. This approach is linked to the highest rates of disease-free survival, overall survival, and the lowest complication rates. However, further high-quality randomized trials are necessary to accurately assess the efficacy of this integrated approach in managing various cancer types.