Data regarding the molecular epidemiology, clonal diversity, and resistance mechanisms of methicillin-resistant Staphylococcus aureus (MRSA) causing skin and soft tissue infections (SSTIs) in Egypt remain limited. This study aimed to characterize the clonal structure, resistance determinants, and virulence profiles of MRSA isolates from SSTIs in Alexandria, Egypt. We analyzed 38 non-duplicate MRSA isolates recovered between July and December 2024 from SSTI specimens submitted to a central microbiology laboratory serving hospitals and outpatient clinics in Alexandria, Egypt. Molecular characterization of antimicrobial resistance, virulence, and biofilm-associated genes were performed using DNA microarray analysis, assigning isolates to clonal complexes (CCs). The diagnostic performance of lateral flow assays (LFAs) for penicillin–binding protein 2a (PBP2a) and Panton–Valentine leukocidin (PVL) detection was evaluated against microarray results. Ten distinct CCs were identified, predominantly CC152 (28.9%) and CC1153 (23.7%). A high prevalence of PVL genes (lukS-PV/lukF-PV) was detected (78.9%), demonstrating significant lineage specificity (p < 0.001) among CC152, and CC1153. Analysis of the antimicrobial resistance gene profiles revealed a broad genotypic resistance repertoire across the collection. Notably, 78.9% carried the fusidic acid resistance gene fusC and 71.1% carried the aminoglycoside resistance gene aacA-aphD, both significantly associated with CC152 and CC1153 (p < 0.001). One isolate (2.6%; lineage CC1-MRSA-[V/VT + fus+ccrAB1]) was confirmed as vancomycin-resistant (VRSA). LFAs demonstrated 100% concordance with microarray results for both PBP2a and PVL detection. This study demonstrates a high prevalence of PVL-positive, multidrug-resistant MRSA lineages among SSTI isolates in Alexandria. The frequent detection of CC152 and CC1153 lineages co-carrying mobile genetic element (MGE)-borne resistance genes (fusC and aacA-aphD) highlights the expansion of multidrug resistance profiles among community-associated genetic backgrounds. Furthermore, the detection of a sporadic VRSA strain emphasizes the necessity of routine phenotypic susceptibility testing alongside molecular screening. The 100% concordance of LFAs supports their implementation as rapid, culture-based screening tools in laboratory diagnostic workflows to guide empirical antibiotic therapy and infection control.