<p>The growing number of cancer cases and deaths highlights the urgent need for innovative treatment approaches. One technique that has lately been recognized as having potential to improve the existing cancer immunotherapy treatment is drug repurposing. By utilizing previously studied molecules that have safety data yet provide superior solutions beyond those of the conventional treatments, it will essentially speed up medication discovery. By influencing the tumor microenvironment, encouraging T cell activation, and thwarting resistance mechanisms, repurposed medications may increase the efficacy of immune checkpoint inhibitors (ICIs). Notable medications include RANKL inhibitors, which boost immune cell responses; TGF-β inhibitors, which improve T cell infiltration; and metformin, which activates cytotoxic T lymphocytes. Other substances, such as GM-CSF and thymosin α1, have also been demonstrated to enhance antitumor immunity in a number of ways by encouraging T-cell activity and dendritic cell maturation. On the other hand, aspirin may enhance immune checkpoint inhibitors by blocking the immunological milieu that tumors produce. Even with the encouraging outcomes of preclinical research and continuing clinical trials, there are still a number of obstacles to overcome in order to optimize dosage strategies, reduce the possibility of off-target effects, and navigate the intricate regulatory environment. Future developments in personalized medicine and artificial intelligence may increase the efficacy of drug repurposing in cancer treatment. To fully realize the potential of repurposed medications in enhancing the results for cancer patients, interdisciplinary cooperation between the academic community, business leaders, and regulatory bodies will be required.</p>