Background: Enhancing nurse managers' awareness and innovation through design thinking is critical for advancing healthcare leadership and improving patient outcomes. A quasi-experimental design was employed, utilizing pre-test and post-test to assess knowledge and an observational checklist to measure innovative managerial skills. The study was conducted at the National Heart Institute, Egypt, with 30 nurse managers participating. Results revealed a highly statistically significant improvement in design thinking knowledge across program phases, as demonstrated by ANOVA (F=23.32, p=0.00) and Chi-square analysis (χ2=29.57, p=0.00). While a slight decline in knowledge was observed during the follow-up phase, levels remained above the baseline. Additionally, the innovative managerial skills of nurse managers significantly improved, with mean percentages reaching satisfactory levels of 90% post program and 76.3% at follow-up, compared to an unsatisfactory preprogram baseline. Conclusion: The program effectively enhanced nurse managers’ knowledge and innovative skills, demonstrating its value in improving managerial competencies in healthcare settings.