Background: Hand hygiene (HH) is the simplest and most effective way to reduce the incidence of healthcare-associated infections (HCAIs). Methods: This cross-sectional study aimed to determine factors associated with self-reported HH performance among nurses at Kelantan tertiary care hospitals. A sample of 438 registered nurses was selected through a stratified random sampling method. Self-reported HH performance was assessed using a validated WHO self-administered HH knowledge and perception questionnaire for healthcare workers. Results: A multiple linear regression analysis was performed to identify the predictors. The factors that significantly predicted self-reported HH performance among nurses included perception score (beta coefficient (β) = 0.260; 95% CI: 0.200, 0.417; p < 0.001), pediatric department (β = −0.104; 95% CI: −9.335, −2.467; p < 0.001), and orthopedic department (β = −5.957; 95% CI: −9.539, −0.720; p < 0.023), adjusted R2 = 0.102; p < 0.001. Nurses with a strong perception and belief in HH were more likely to have better HH performance. Compared to pediatric and orthopedic, surgical departments were associated with better self-reported HH performance. Conclusions: This study showed the importance of factors that could improve the intervention’s performance in HH strategy. Lack of perception and HH program intervention in departments engaged in patient care could lead to poor HH practices, thus increasing HCAIs and antimicrobial resistance (AMR).