Fusarium wilt of banana, caused by Fusarium oxysporum f. sp. cubense (Foc), particularly the virulent tropical race 4 (TR4), remains a critical threat to global banana production. Conventional control strategies, including chemical treatments and quarantine measures, have been largely ineffective due to the pathogen’s soilborne persistence. This review highlights recent biotechnological innovations offering sustainable solutions for disease management. Advances in genomic tools, genetic engineering, RNA interference, and microbial biocontrol have demonstrated significant potential, with transgenic and CRISPR/Cas9-edited banana cultivars exhibiting enhanced resistance to Foc. Additionally, beneficial microbes such as Trichoderma spp. strengthen host defenses, while high-throughput technologies, including artificial intelligence and big data analytics, enable early detection and real-time monitoring of disease outbreaks. However, challenges such as regulatory hurdles, insufficient field validation, and evolving pathogen virulence hinder widespread implementation. A multidisciplinary approach integrating biotechnology with sustainable agronomic practices is crucial for long-term mitigation. Strengthening global collaboration and fostering continued innovation are imperative to protect banana production, ensuring food security and economic stability worldwide.