Methicillin-resistant Staphylococcus aureus is raising global concern as it overcomes immune challenges through various virulence mechanisms.

Methicillin-resistant Staphylococcus aureus (MRSA) in the 21st century remains a global concern with increasing rates of morbidity and mortality in healthcare settings. Hospital-associated MRSA strains have developed multidrug resistance (MDR), limiting the effectiveness of several commonly used antibiotics. First-line treatment for MRSA depends on the type of infection caused. Antibiotics such as vancomycin, linezolid, and daptomycin remain central to managing serious MRSA infections. However, the rise of MDR and the need to prevent further antibiotic resistance have led to the use of combinational antibiotic regimens to manage serious infections. Furthermore, MRSA can acquire virulence determinants and resistance plasmids via mobile genetic elements (MGEs) and stably inherit diverse resistance mechanisms, fostering hypervirulent MDR lineages that complicate clinical management. Together, these factors enable MRSA to evade host immune defences and cause serious infections with poor clinical outcomes. Collectively, this review highlights the epidemiological burden of MRSA with a better understanding of its resistance and virulence mechanisms and reinforces the need for optimized approaches to prevent, manage, and control infections.