Objective <p>To investigate the current status of Nurse Innovative Behavior and explore its influencing factors, so as to provide a reference for intervention studies.</p> Methods <p>A cross-sectional survey was conducted in June 2025 using convenience sampling to select 654 clinical nurses. The Nurse Innovative Behavior Scale, Perceived Organizational Support Scale, and Change Fatigue Scale were used for questionnaire investigation.</p> Results <p>The total score of Nurse Innovative Behavior was 34.00 (30.00, 40.00), based on a theoretical range of 12–48 points on the Innovative Behavior Scale, where scores between 30 and 40 represent the moderate to high range, indicating a moderate-to-high level; the total score of Perceived Organizational Support was 52.00 (49.00, 65.00), also at a moderate-to-high level; the score of Change Fatigue was 24.00 (20.00, 30.00), suggesting that nurses generally experienced moderate levels of change fatigue. Correlation analysis showed that Innovative Behavior was significantly positively correlated with Perceived Organizational Support (<i>r</i> = 0.376, <i>p</i> &lt; 0.01) and negatively correlated with Change Fatigue (<i>r</i> = -0.082, <i>p</i> &lt; 0.05). Multiple regression analysis revealed that Professional Learning Time (Hours/Day) (β′ = 0.108, <i>p</i> = 0.003) and Perceived Organizational Support (β′ = 0.328, <i>p</i> &lt; 0.001) had significant positive effects on Innovative Behavior. Although Change Fatigue did not reach statistical significance (<i>p</i> = 0.068), it showed a negative trend. The regression model accounted for 17.8% of the variance in innovative behavior (adjusted R² = 0.178).</p> Conclusion <p>This study identified Perceived Organizational Support and dedicated Professional Learning Time as significant positive predictors of Nurse Innovative Behavior (NIB). A key finding was that the beneficial effect of organizational support was significantly attenuated by higher levels of Change Fatigue, indicating its role as a critical boundary condition. While Change Fatigue showed a direct negative trend, its primary clinical significance appears to lie in this moderating effect. These insights, consistent with theories on resource conservation and the documented challenges of implementing change in complex settings, suggest that strategies to foster innovation must be dual-focused. Healthcare institutions should concurrently strengthen organizational support and proactively manage change processes to mitigate fatigue. Future research should employ longitudinal designs to confirm causality and explore how variables like leadership style can preserve innovative capacity amidst operational pressures.</p>