Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of community- and hospital-acquired infections which poses serious therapeutic challenges. This study aimed to evaluate the resistance patterns and genomic characteristics of S. aureus isolates from a tertiary care hospital in India. A total of 3,266 clinical specimens were processed from January 2023 to December 2024, of which 425 (13%) were S. aureus. Among them, 55.2% were MSSA and 44.8% were MRSA. MRSA isolates were categorized as community-acquired (CA-MRSA, 82.14%) or hospital-acquired (HA-MRSA, 17.85%) based on clinical data. MRSA was most frequently isolated from pus (56.8%) and wound swab (33.6%) samples. Infections were more common in men and patients aged 41-60 years. The prevalence was significantly higher in patients with diabetes (30%) than in those without diabetes (9%) (p = 0.04). PVL was detected in 63.6% of MRSA, with higher expression in CA-MRSA. The mecA gene was found in 97% of MRSA isolates, whereas mecC was present in 1.5% of isolates. MRSA showed high resistance to penicillin (100%), ciprofloxacin (70.5%), and cotrimoxazole (60%), but remained sensitive to vancomycin. MDR was observed in 96% of MRSA and 18.1% of MSSA. Inducible clindamycin resistance was detected in 54.7% of MRSA isolates. Biofilm production was noted in 49.4% of MRSA isolates, with icaA and icaD genes detected in 19% of them (p = 0.001). This study highlights the high prevalence of CA-MRSA, with significant resistance patterns and virulence markers. Continued surveillance is essential for effective infection control and ensuring antibiotic stewardship.