Abstract: Hand hygiene is universally acknowledged as the most effective and low-cost measure for preventing healthcare-associated infections (HAIs). Despite clear evidence, hand hygiene compliance among healthcare workers—particularly surgical nurses—remains below optimal levels. Surgical nurses are pivotal in ensuring aseptic practices, reducing surgical site infections, and safeguarding patients in perioperative and ward settings. However, barriers such as heavy workloads, skin irritation, inadequate resources, insufficient knowledge, time pressures, and organizational culture hinder effective adherence to recommended protocols. This paper critically examines these barriers and explores potential solutions, including education, infrastructural support, behavior change interventions, and leadership engagement. It further highlights innovative strategies such as electronic monitoring systems and multimodal interventions to strengthen compliance. The discussion underscores the need for a holistic, system-wide approach where institutional accountability and individual responsibility work hand-in-hand. Improving surgical nurses’ compliance not only enhances patient safety but also reduces healthcare costs and strengthens infection control measures.