<p>Neonatal hyperbilirubinemia is a common clinical condition that, if not promptly and effectively managed, may lead to rare but severe neurodevelopmental complications. This review traces the historical progression of screening, diagnostic, and therapeutic approaches, highlights current standards such as phototherapy and immunotherapy, and examines emerging innovations including artificial intelligence and novel pharmacologic agents. It also addresses persistent global health disparities and explores future directions in research and precision medicine. A comprehensive literature search was conducted using PubMed, Scopus, and Cochrane databases, focusing on studies related to epidemiology, diagnostic strategies, and clinical management guidelines. Early recognition and intervention are essential to prevent both acute and long-term consequences. While phototherapy remains the mainstay of treatment, other adjunctive therapies are increasingly utilized in high-risk populations. Advances in screening and diagnostic technologies are reshaping individualized care, particularly in low-resource settings. Achieving global equity in neonatal jaundice outcomes requires technological advancement coupled with coordinated policy efforts, health system investment, and cross-sector collaboration to reduce preventable deaths and disability worldwide.</p><p> <i>Conclusion</i>: Timely recognition and management of neonatal hyperbilirubinemia remain essential to prevent adverse outcomes. Advances in diagnostics, therapeutics, and global implementation strategies offer promising avenues to improve care and reduce disparities across diverse healthcare settings to reduce neonatal morbidity and mortality.</p>