Abstract Background Innovation enables nurses to improve care delivery, yet their role is rarely recognized. The work activities in innovative work behavior (IWB) are characterized by their dynamic nature, involving complex tasks that are not standardized or routine in nature. This study examined the relationships between creative self-efficacy (CSE), trust in supervisors, uncertainty avoidance, psychological capital, and innovative work behavior among Egyptian nurses. Methods A cross-sectional correlational design was employed. A convenience sample of 310 nurses (mean age=31.52±8.21 years), of both genders and aged above 18 years, was recruited at Assiut University Hospital. Data were collected using a structured questionnaire including demographic and work-related data, the Creative Self-Efficacy Scale, Trust in Supervisor Scale, Uncertainty Avoidance Scale, Psychological Capital Questionnaire, and Innovative Work Behavior Scale. Data were analyzed using descriptive statistics, Pearson correlation coefficients, and multiple linear regression analysis. Results Using convenience sampling, participants were categorized into low, moderate, and high IWB groups. The findings demonstrated that higher levels of innovative work behavior were associated with higher levels of creative self-efficacy, uncertainty avoidance, and psychological capital. Significant positive correlations were observed between IWB and all studied psychological variables. Multiple regression analysis revealed that creative self-efficacy, uncertainty avoidance, and psychological capital were significant predictors of innovative work behavior, whereas trust in supervisors did not retain statistical significance. Conclusions The results highlight the multifaceted psychological determinants of innovative work behavior in nursing practice the findings suggest that strengthening nurses’ creative self-efficacy, psychological capital, and adaptive responses to uncertainty may enhance innovative work behavior.