Background: Artificial intelligence applications have grown vastly across all aspects of healthcare. Nursing practice is critical and AI technology will enhance practice and pediatric patient outcomes. The current study aimed to evaluate the effect of orientation programs on pediatric nurses' knowledge and perception regarding the application of artificial intelligence. Design: To fulfill the aim of this study a quasi-experimental design was utilized. Setting: This study was conducted in pediatric departments at Sohag University Hospitals. Sample: A convenience sample included (100) nurses were selected from the previously mentioned settings. Tools: Two tools were used to collect the data: Nurses' Knowledge regarding the Artificial Intelligence Questionnaire and Nurses' Perception regarding the application of artificial intelligence. Results: The current study results revealed that there was a highly statistically positive correlation between total knowledge and perception among pediatric nurses. Moreover, highly statistically significant differences between total knowledge and perception level post-orientation program (P<0.001). Conclusion: This study concluded that the orientation program had a significant positive effect on improving the studied nurses' knowledge and perception regarding the application of artificial intelligence. Recommendation: Encourage nurses to increase their knowledge and perception toward artificial intelligence through attendance workshops and training programs regarding artificial intelligence applications, which are required to enable them to integrate artificial intelligence applications into nursing practices.