Background Emphasizing the crucial significance of maintaining a national nursing workforce well-prepared with the necessary knowledge, skills, and abilities to respond effectively is the growing frequency of natural and environmental disasters, coupled with public health emergencies such as the COVID-19 pandemic. So, the study aimed to explore pediatric nurses' preparedness to monkeypox outbreak, and their stress during this outbreak in Egypt. Methods A cross-sectional study was conducted on a 416 nurses direct care for children at selected governmental hospitals in Egypt. Demographic form, Questionnaire for Infectious Disease Outbreak Readiness & Preparedness, factors affecting nurses' preparedness, and the generalized anxiety disorders scale-7 were the tools of the study. Results (81.5%) of studied nurses had unsatisfactory level of preparedness to monkeypox outbreak. (96.4%) and (95.4%) of them were affected their preparedness by high workload and inconsistent income with the of risk of infection factors. Also, (57.2%) of them had high stress level. Conclusions The study revealed the importance of ensuring adequate supplies of PPE are available and provided, and protocols must be implemented to ensure availability in case of an outbreak. Moreover, nurse staffing levels and workload distribution should be regularly reviewed to create reasonable nurse-patient ratios. © 2024 Sadek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.