Abstract: Pain is a complex and multidimensional experience that significantly affects neonates and children during hospitalization, medical procedures, and chronic illness management. Historically, pediatric pain was underestimated due to misconceptions regarding immature nervous systems and limited communication abilities. Contemporary research has disproved these beliefs, emphasizing that untreated pain in early life may have long-term physiological, psychological, and developmental consequences. This review critically examines evidence-based strategies for pain assessment, pharmacological and non-pharmacological management, and the role of healthcare professionals, particularly nurses, in optimizing pediatric pain care. It synthesizes current guidelines, clinical practices, and recent research findings to provide a comprehensive framework for improving pain management outcomes in neonates and children. The review highlights ethical considerations, family-centered approaches, and emerging innovations to support holistic, safe, and effective pain management in pediatric settings.