We aimed to determine the prevalence of antimicrobial resistance, carriage of Panton-Valentine leucocidin (PVL), and the clonal structure of MRSA isolates collected from skin and soft tissue infections at a tertiary care hospital in Pakistan. Between August 2021 and May 2022, 154 non-repetitive MRSA isolates were consecutively collected and characterized by antimicrobial susceptibility testing, SCCmec typing, spa typing, and detection of PVL by PCR. MLST clonal complexes (CCs) were inferred from spa type using the Based Upon Repeat Pattern (BURP) algorithm. High levels of resistance were observed to ciprofloxacin (85.7%), erythromycin (76.0%), sulfamethoxazole (68.8%), gentamicin (68.8%), fusidic acid (57.8%), tetracycline (55.8%), and clindamycin (42.2%). Clonal analysis revealed 16 lineages, with the most frequent being CC8-MRSA-IV (27.3%), PVL-positive “Bengal Bay” CC1/ST772-MRSA-V (26.0%), and CC1-MRSA-IV (16.2%). PVL was detected in 45.5% of isolates across multiple lineages. Our findings highlight the coexistence of high antimicrobial resistance and frequent PVL carriage among MRSA in Pakistan. Given the association of PVL with severe infections and the limited treatment options for multidrug-resistant strains, these data underscore a significant public health concern and the need for systematic surveillance and prudent antibiotic use.