Foot-and-mouth disease virus (FMDV) remains a major threat to livestock in Egypt, with ongoing outbreaks involving serotypes A, O, and SAT2. This study aimed to improve the understanding of these circulating FMDV strains to improve control measures. Between 2022 and 2023, 134 cattle samples from across Egypt were analyzed, revealing a 67.9% positivity rate for Pan FMDV. Of these positive samples, 64 were identified as serotype A and 27 as serotype O. Genetic analysis indicated that serotype O strains clustered within the EA-3 topotype, suggesting endemic persistence and potential vaccine evasion, while serotype A strains were associated with the African topotype and linked to regions such as Ethiopia, Kenya, and Sudan. Notable amino acid mutations in the VP1 protein of both serotypes highlighted potential challenges to vaccine effectiveness. These findings underscore the need for enhanced surveillance, timely vaccine updates, and regional cooperation to effectively manage FMD outbreaks in Egypt and neighboring countries.