Background: Acute poisoning in children aged 1–5 years is a critical global health concern and a leading cause of accidental mortality. Nurses often serve as the first point of contact for children with acute poisoning, highlighting the importance of their role in providing effective care. Aim: The aim of this study was to evaluate the impact of an educational program on improving nurses' knowledge and practices in caring for poisoned preschool-aged children. Design: A quasi-experimental design was conducted at Zagazig Poison Control Center, Zagazig University Hospitals, and Zagazig General Hospital, involving all 40 nurses working in these centers and 80 children. Tools: three tools were included the first, a structured interviewing questionnaire, the second, an assessment of nurses' knowledge on pediatric poisoning, and the third an observational checklist for pediatric nursing procedures. Results: Findings revealed that prior to the program, 70% of nurses had poor knowledge and 85% exhibited unsatisfactory practices. Following the program, 92.5% demonstrated good knowledge, and 95% achieved satisfactory practices. A significant positive correlation was observed between knowledge and practice scores pre- and post intervention. Conclusion: The study concluded that the educational program significantly improved nurses' performance in managing poisoned preschool-aged children. Recommendation: It is recommended to implement periodic evaluations and training to continually update nurses’ skills and knowledge in acute poisoning management.