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Staphylococcus aureus is a major public health concern and is classified as a priority pathogen by the World Health Organization (WHO) with the global rise of methicillin-resistant S. aureus (MRSA) infections. Community-associated MRSA (CA-MRSA) strains have become increasingly important in both community and healthcare settings. This study aimed to investigate the genomic diversity, evolution, resistome, and virulome of CA-MRSA isolates circulating in Egypt to better understand their persistence, adaptation, and public health implications. A total of 123 CA-MRSA isolates were collected from clinical settings in Alexandria, Egypt. Methicillin resistance was first determined phenotypically using cefoxitin resistance, followed by genotypic confirmation through detection of the mecA gene.Whole-genome sequencing and comparative genomic analyses were performed to characterize sequence types, clonal complexes, SCCmec elements, resistance determinants, and virulence factors. Phylogenetic relationships were reconstructed to assess evolutionary divergence, and network analysis was used to explore associations between resistance and virulence gene profiles. Eight distinct clonal complexes (CCs) were identified, dominated by CC121-SCCmecV (15%), CC1-SCCmecV (14%), CC15-SCCmecV (9%), CC1-SCCmecVI (7%), and CC8-SCCmecV (6%). Five novel sequence types (ST8157–ST8161) were discovered and deposited in pubMLST, indicating ongoing local evolution. Within CC8, two divergent lineages (ST239 and ST8) harbored unique SCCmec elements, reflecting significant phylogenetic differentiation. Globally important epidemic clones such as ST239-III-MRSA and ST22-IV-MRSA (EMRSA-15) were also detected. Network analysis revealed broad ecological adaptability, with livestock-associated CC97 and healthcare-associated CC5 harboring genes for immune evasion and biofilm formation. The detection of yopB in CC97 and yscT in CC5, genes typically found in Yersinia species, suggests horizontal gene transfer as a mechanism of adaptation. The high prevalence of fosB (fosfomycin resistance) and elevated fusidic acid resistance (39%) further underscores the emergence of multidrug resistance. This large-scale genomic analysis reveals the coexistence of globally disseminated and locally evolved CA-MRSA lineages in Egypt. The findings underscore the adaptive potential of Egyptian MRSA populations and their contribution to regional AMR dynamics. Continued genomic surveillance within a One Health framework is essential for monitoring MRSA evolution, informing control measures, and mitigating the spread of resistance in both community and clinical settings. Not applicable.