¹Department of Veterinary Medicine, University of Veterinary and Animal Sciences, 54000, Lahore - PAKISTAN DOI : 10.9775/kvfd.2026.36030 Antimicrobial-resistant Staphylococcus aureus particularly methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide challenge for both veterinary and human health. This study investigated MRSA in respiratory tract infections of cats, associated risk factors, antibiogram profiling and synergy testing for resistance modulation. A total of 103 nasal swabs collected from cats were processed to identify and confirm S. aureus and MRSA using microbiological, biochemical, and molecular tests. Furthermore, antibiogram profiling and in-vitro trials for resistance modulation against MRSA were also conducted. The molecular prevalence of S. aureus in respiratory tract infections in cats was 37.86%. Among infected cats, phenotypic and genotypic prevalence of MRSA was 64.10% and 38.46%, respectively. Antibiotic susceptibility trials against MRSA revealed highest resistance against Ceftriaxone, Cefixime, and Penicillin G (100%). Resistance modulation trials revealed synergism between Ceftriaxone with Ketoprofen against MRSA. Risk factors analysis revealed significant association including respiratory illness, housing hygiene, human contact, and diagnostic resources. Phylogenetic analysis of mecA sequences revealed four study isolates (PP768062, PP852380, PP848319, PP848320) showing significant similarity with each other and with mecA sequences already reported from Myanmar and Pakistan, while one isolate (PP848321) showed significant similarity with mecA from Nigeria, India, Pakistan, and Iraq. The study provided useful insights into resistance profiling and resistance modulation to tackle challenge of antimicrobial resistance in S. aureus. Keywords : Antimicrobial resistance, Molecular characterization, MRSA, Phylogenetic analysis, Staphylococcus aureus