Background <p>The proactive personality of nursing students is considered a key factor in fostering innovative behaviors, which are essential for the advancement of nursing practice and research. However, the mechanism through which a proactive personality influences innovative behavior is not well understood. Deep learning approach, characterized by critical thinking and engagement with complex concepts, is posited as a potential mediator.</p> Objectives <p>This study aims to explore the relationship between proactive personality and innovative behavior among undergraduate nursing students and to determine the mediating effect of deep learning approach in this relationship.</p> Methods <p>A cross-sectional survey design was utilized for this study. Data were collected from a convenience sample of 1885 valid undergraduate nursing students using validated scales to measure proactive personality, deep learning approach, and innovative behavior. The survey was administered electronically from March to May in 2024. The hypothesized mediating role of deep learning approach was tested using PROCESS with SPSS software.</p> Results <p>The results indicated that undergraduate nursing students’ proactive personality was found to have a significant positive correlation with their deep learning approach (<i>r</i> = 0.861, <i>p</i> &lt; 0.001) and innovative behavior (<i>r</i> = 0.862, <i>p</i> &lt; 0.001). Positive associations were found between deep learning approach and innovative behavior (<i>r</i> = 0.843, <i>p</i> &lt; 0.001). Deep learning approach played a 38.98% mediation effect between proactive personality and innovative behavior.</p> Conclusion <p>The study provides evidence for the mediating role of deep learning approach in the relationship between proactive personality and innovative behavior among undergraduate nursing students. These findings underscore the importance of educational strategies that promote deep learning approach to enhance the innovative potential of nursing students.</p>