Purpose <p>This systematic review investigates drug repurposing as a strategy to accelerate and improve cancer treatment by specifically examining how existing medications can effectively target the established hallmarks of cancer. The research explores how repurposed drugs can address the challenges of conventional cancer drug development, including high costs, lengthy development timelines, and frequent clinical failures.</p> Methods <p>The review systematically analyzes repurposed drugs with their ability to target specific cancer hallmarks, including oncogenic signaling pathways, cell death regulation, metabolic reprogramming, growth suppressor reactivation, phenotypic plasticity, antitumor immunity, telomerase activity, angiogenesis, inflammation, cellular senescence, invasion and metastasis, DNA damage response, microbiome modulation, and epigenetic regulation.</p> Results <p>The analysis identified several promising repurposed medications targeting specific cancer hallmarks: artemisinin derivatives for oncogenic signalling, niclosamide for cell death pathways, leflunomide for metabolic dysregulation, statins for tumour suppressor reactivation, metformin for phenotypic plasticity, liothyronine for immune activation, PARP inhibitors for replication, itraconazole for angiogenesis, celecoxib for inflammation, BCL-2 inhibitors for senescence, fluoroquinolones for metastasis, spironolactone for DNA damage, isoliquiritigenin for microbiome modulation, and various agents targeting non-mutational epigenetic regulation.</p> Conclusion <p>Drug repurposing represents an intriguing approach for addressing the limitations of traditional cancer drug development while effectively targeting the fundamental hallmarks of cancer. By leveraging existing medications with established safety profiles, this strategy offers potential for more rapid translation to clinical applications and may enhance the therapeutic arsenal against various cancer types.</p>