Significant advancements have been made in cancer therapy; however, limitations remain with some conventional approaches. Adjuvants are agents used alongside primary treatments to enhance their efficacy and the treatment outcomes of patients. Modern lifestyles contribute to deficiencies in melatonin and vitamin D. Limited sun exposure affects vitamin D synthesis, and artificial light at night suppresses melatonin production. Both melatonin and vitamin D possess anti‑inflammatory, immune‑boosting and anticancer properties, rendering them potential adjuvants of interest. Studies suggest melatonin and vitamin D supplementation may address antioxidant imbalances in lip, oral and pharyngeal cancers. Moreover, promising results from breast, head and neck, brain, and osteosarcoma research indicate potential for tumor growth inhibition, improved survival, and a better quality of life of patients with cancer. The radioprotective properties of melatonin and vitamin D are another exciting area of exploration, potentially enhancing radiotherapy effectiveness while reducing side effects. For its part, the sleep‑promoting effects of melatonin may indirectly benefit patients with cancer by influencing the immune system. Thus, the prevalence of vitamin D and melatonin deficiencies highlights the importance of supplementation, as lower levels can worsen side‑effects from cancer treatments. The present review explores the potential of combining melatonin and vitamin D as synergistic adjuvants for cancer therapy. These agents have shown promise individually in cancer prevention and treatment, and their combined effects warrant investigation. Therefore, large‑scale controlled trials are crucial to definitively determine the optimal dosage, safety and efficacy of this combination in improving the lives of patients with cancer.