Background: Infections caused by S. aureus strains encoding Panton-Valentine leukocidin (PVL-SA) have become increasingly relevant in community settings and can cause severe conditions in pediatric populations. We present a pediatric case of invasive disease caused by PVL-SA and provide a literature review of severe manifestations caused by these strains in children. Methods: A PubMed search (February 2024) evidenced studies that included relevant clinical outcomes, diagnostics, and treatments, excluding cases of asymptomatic infection or adult populations. Logistical multivariate analysis was used to find predictors of the need for intensive care. Results: A 10-year-old boy came to the attention of our Pediatric Infectious Diseases Unit with fever, chest pain, and tachypnea. A rapid worsening of his clinical conditions was observed, with the development of necrotizing pneumonia, osteomyelitis, deep vein thrombosis (DVT), and multiple abscesses. Blood cultures confirmed the presence of PVL-producing methicillin-resistant S. aureus (MRSA). The initial treatment included linezolid and ceftaroline and was later adjusted to clindamycin, daptomycin, and fosfomycin, with clinical improvement. Discussion: Our review collected 36 articles, including 156 pediatric cases of severe PVL-SA infection. Bacteremia was present in 49% of cases, lung infection in 47%, and osteomyelitis in 37%. The presence of pulmonary localization was predictive of the need for intensive care, O.R. 25.35 (7.46 - 86.09; p<0.001). Anti-toxin molecules were used in about half the cases where information on treatment was reported. Our report highlights the capacity of PVL-SA to cause life-threatening complications in children, while also discussing the full range of its clinical spectrum and the most effective therapeutic approaches.