Pyomyositis and osteomyelitis are rare but serious infections of soft tissues and the musculoskeletal system in infants, particularly when caused by Methicillin-resistant Staphylococcus aureus (MRSA). We present a case involving MRSA pyomyositis and osteomyelitis following intramuscular hepatitis B vaccination in a 30 day-old male. The infant exhibited increasing swelling and pain in the left thigh three days post-vaccination. Imaging revealed an intramuscular abscess and early signs of osteomyelitis. Cultures from pus and tissue confirmed MRSA. The infant was treated with surgical drainage, debridement, and intravenous vancomycin, leading to a positive recovery. This case highlights the critical need for strict aseptic procedures during vaccination and early recognition and management of rare post-vaccination infections in infants to prevent serious outcomes.