<div><p>Vibrio cholerae remains a significant public health threat in Sub-Saharan Africa and the East Mediterranean Region, where recurrent outbr eaks ar e dri v en by inadequate w ater, sanitation, and hygiene infrastructur e, climatic v aria bility, and socio-political instability. This re vie w e xplores the persistence of the patho g en in these reg ions, e xamining its epidemiolo gy, environmental reservoirs, and genomic adaptations that enhance its survi v al and transmission. We highlight the impact of antimicr obial r esistance and the role of climate change in cholera dynamics. Furthermore, we discuss current prevention and control str ate gies, including ad vancements in or al c holer a v accines, genomic surv eillance, and micr obiome-targeted interv entions. Addr essing these challenges r equir es a m ultifaceted approach that integrates sustaina b le sanitation impr ov ements, str engthened disease surv eillance, and innov ati v e v accination str ate gies. Understanding the persistence of V. cholerae in these high-risk regions is critical for developing effective, long-term mitigation str ate gies to reduce c holer a morbidity and mortality.</p></div>