Cancer remains a formidable global health burden, with conventional chemotherapy often limited by factors such as systemic toxicity, drug resistance, and challenges related to patient adherence. In this context, food and medicine homology (FMH) substances, rooted in the principles of Traditional Chinese Medicine, offer a distinctive therapeutic paradigm by integrating pharmacological efficacy with nutritional value. Defined by their low toxicity and suitability for long-term use, these substances present a compelling avenue for the development of safer and more integrative oncology strategies. This review provides the first systematic and comprehensive analysis of the role of these substances across the full spectrum of pan-cancer management, encompassing tumor prevention, adjunctive therapy, and postoperative nutritional support. At the mechanistic level, we elucidate their pleiotropic modes of action, including antioxidant activity through free radical scavenging and metal chelation, anti-inflammatory effects via modulation of key signaling pathways, immune enhancement, and direct antitumor activities. In addition, these substances function as effective adjuvants to chemotherapy and radiotherapy, enhancing therapeutic efficacy, reducing adverse effects, and helping to overcome drug resistance. By integrating molecular evidence, preclinical findings, and emerging clinical insights, this review bridges traditional knowledge with contemporary science, thereby laying a solid foundation for the clinical translation of these substances. It not only fills a critical gap in the systematic understanding of their application across diverse cancer types but also outlines a comprehensive framework for the development of safer and more effective integrative oncology strategies.