This comprehensive learning activity examines neonatal hypoglycemia as a potentially serious metabolic condition affecting 5-15% of healthy term newborns and up to 50% of at-risk infants. It explores the pathophysiology of glucose homeostasis during the transition from fetal to neonatal life, detailing how newborns mobilize compensatory mechanisms to maintain euglycemia after birth. It provides evidence-based guidelines for identifying at-risk neonates through maternal and infant risk factors, and outlines clinical assessment strategies to recognize subtle and often non-specific symptoms of hypoglycemia. The material presents a tiered approach to management, from preventive strategies like early feeding and skin-to-skin contact to interventions for symptomatic or severe cases requiring IV glucose therapy. Additionally, it addresses interdisciplinary collaboration, sociocultural considerations, and long-term neurodevelopmental outcomes. Throughout, the instruction emphasizes the critical role of nursing vigilance in early detection and intervention while balancing technical care with family-centered principles.