Background: Neonates, inherently vulnerable due to low birth weight, physiological immaturity, and extensive medication exposure, are at an increased risk of iatrogenic skin harm. Aim of the study: The study aimed to evaluate effectiveness of an educational program on iatrogenic skin afflictions, focusing on pediatric nurses' performance and neonates' clinical outcomes. Methods: Conducted at the Neonatal Intensive Care Unit (NICU) of Aswan University hospital, the quasi-experimental study involved a convenient sample of 55 nurses and 39 neonates admitted within one month. Data collection utilized three tools: a structured interview questionnaire encompassing biosocial data and nurses' knowledge, an observation checklist to assess nurse practices regarding iatrogenic skin affliction, and an assessment of neonate clinical outcomes. Results: Post-educational program, the study revealed significant improvements in both nurses' knowledge and practices. Statistically significant differences were observed in nurses' knowledge and practices before, immediately after, and one month after the educational program. Conclusion: Implementation of an educational program addressing skin injuries resulted in improved nurses' performance in Neonatal Intensive Care Units. Integrating preventive care measures for acquired skin injuries into routine neonatal care is highly recommended. Practical Implications: Highlighting neonatal vulnerability to iatrogenic skin issues, the NICU education program proved crucial for nurses. Post-program, enhanced knowledge and practices were noted, emphasizing the practical significance of targeted education to mitigate iatrogenic risks in neonatal care settings. for targeted neonatal education to mitigate iatrogenic risks.