Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) pose significant challenges in Nigerian healthcare facilities, exacerbated by inadequate infection control measures. Despite efforts by the National Centre for Disease Control (NCDC), the implementation of infection prevention and control (IPC) measures remains suboptimal, as evidenced by Nigeria’s Joint External Evaluations (JEE) IPC score. A system-thinking approach is essential to address the interconnected challenges in the healthcare system, including governance, human resources for health (HRH), and health information. It recognizes that IPC is not a standalone programme but deeply interconnected with the broader healthcare system.