Methicillin-resistant Staphylococcus aureus (MRSA) surveillance in regions with mass gatherings presents unique challenges for public health systems. Saudi Arabia, hosting millions of pilgrims annually, provides a distinctive setting for studying how human mobility shapes bacterial populations, yet comprehensive genomic surveillance data from this region remains limited. Here, we present an integrated analysis of S. aureus isolates collected across seven Saudi Arabian regions, combining whole-genome sequencing with extensive antimicrobial susceptibility testing and standardized metadata capture. Our analysis revealed striking differences between pilgrimage and non-pilgrimage cities. Pilgrimage cities showed significantly higher genetic diversity and antimicrobial resistance rates, harboring numerous international strains including recognized clones from various geographic origins. While genomic prediction of antimicrobial resistance showed high accuracy for some antibiotics, particularly beta-lactams, it performed poorly for others, highlighting the ongoing need for phenotypic testing in clinical settings. Our findings demonstrate how mass gatherings shape bacterial population structures and emphasize the importance of integrated surveillance approaches in regions with significant international travel.