Background. Neonatal pain has been underrecognized and undertreated in many settings with the youngest children and neonates suffering the greatest consequences. Despite recent advancements in the assessment and therapy of children’s pain, a knowledge‐to‐practice gap still exists especially in developing nations including our country Ethiopia. Objectives. To assess knowledge, practice, and associated factors towards neonatal pain management among health care professionals working at neonatal intensive care units of public hospitals in North Shoa Zone, Amhara regional state, Ethiopia. Method. Facility‐based cross‐sectional study design was conducted among health care professionals working at NICU in all public hospitals in North Shoa Zone, from May 9, 2023, to May 23, 2023. Data were collected using a self‐administered questionnaire from 123 health care professionals working at NICUs in eleven public hospitals. The collected data were checked and entered into EPI data version 3.1 and then exported to SPSS version 25 for further descriptive and logistic regression analysis. Data are summarized using descriptive statistics and presented using narrations, tables, and graphs. Result. The study reveals that 48% of health care professionals possessed adequate knowledge, while only 5.7% demonstrated good practices in neonatal pain management. Factors significantly associated with better neonatal pain management practices included having good knowledge of neonatal pain management (AOR = 3.36, 95% CI [1.19–9.49]), a higher educational level (AOR = 4.48, 95% CI [1.62–13.88]), and the availability of a pain scale assessment tool in the neonatal unit (AOR = 3.91, 95% CI [1.50–10.20]). Moreover, the type of profession, specifically being a nurse (AOR = 0.23, 95% CI [0.08–0.66]), was significantly associated with knowledge of neonatal pain management. Conclusion. Health care professionals’ knowledge and practice regarding neonatal pain management are insufficient. Multisectoral collaboration is essential to enhance their knowledge and skills and improve the availability of pain scale assessment tools and supportive materials.