Introduction. Methicillin-resistant Staphylococcus aureus (MRSA) represents a significant threat to public health due to its capacity for dissemination, colonization, and resistance to multiple antibiotics. Its distribution among humans, animals, food, and environment emphasizes the need to address it from a “One Health” approach. Objective. To analyze the epidemiology of methicillin-resistant Staphylococcus aureus, including its virulence profile, distribution in different reservoirs, frequency of resistance genes and evaluation of the susceptibility profile. Methodology. A literature review was performed in PubMed, Scopus, and BVS databases, using MeSH terms and Boolean operators, applying the PRISMA method for article selection. Results. Analysis of 26 MRSA-focused studies identified the most prevalent virulence factors as: nuc, hla, hlb, clfA, clfB, coa, ica, and icaD, in addition to enterotoxins seb, sel, seo, and immunomodulatory genes scn, sak, and chp. The highest MRSA prevalence was identified in animal reservoirs (22.8%), followed by human (18.8%), food (7.7%), and environmental samples (4.6%). A high prevalence of the mecA (57.1%) and blaZ (70.7%) genes was observed, whereas the mecC gene was detected at a lower frequency (2.5%). Resistance to cefoxitin, oxacillin, penicillin, and ampicillin was consistently high across all reservoirs. Notably, resistance to vancomycin was detected in animal-derived isolates, representing a significant concern. Nevertheless, linezolid remained highly effective, with negligible resistance observed in the studied reservoirs. Conclusion. Methicillin-resistant Staphylococcus aureus exhibits a broad range of virulence factors and resistance determinants, with considerable prevalence across multiple reservoirs, highlighting its zoonotic potential and the importance of integrated surveillance within a One Health framework. General Area of Study: Health. Specific area of study: Microbiology. Type of study: Systematic bibliographic review.