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In this study, we investigated both meat-derived and methicillin-resistant Staphylococcus aureus (MRSA), exploring their genetic relatedness to patient-derived MRSA isolates in Saudi Arabia. We collected 250 meat samples and identified 53 S. aureus isolates, with 79% being methicillin-sensitive Staphylococcus aureus (MSSA) and 21% being MRSA. Moreover, we included 80 clinically confirmed patient-derived MRSA isolates. We identified the most common S. aureus clone in both patients and retail meat. In meat, ST6 and ST97 were the most common clones in 55% of the MRSA isolates, and ST1153 and ST672 were the most common in 21% and 17% of the MSSA isolates. In patients, ST5 and ST6 were the predominant clones in 46% of the S. aureus isolates. CC5/ST5-SCCmecVc-t311 and CC361/ST672-SCCmecV-t3841 were common MRSA clones in both meat and patients. CC97 and CC361 clones were the second most prevalent S. aureus clones in meat and were relatively common in patients. Furthermore, we sequenced and characterized novel S. aureus strains ST8109, ST8110, and ST8111. The genomic similarities between meat- and patient-derived S. aureus isolates suggest that retail meat might be a reservoir for S.aureus and MRSA transmission. Therefore, a structured One Health approach is recommended for S. aureus dissemination, genetic characterization, antibiotic resistance, and impact on human health. [ABSTRACT FROM AUTHOR]