Neonatal encephalopathy of hypoxic-ischemic origin remains a leading cause of global neonatal mortality. Over the past decades, various neuroprotective strategies have been explored; however, therapeutic hypothermia remains the only clinically approved intervention to date. This review outlines emerging and adjunctive treatment modalities beyond therapeutic hypothermia and emphasizes the critical need for robust and reproducible translational research to bridge the gap between preclinical findings and clinical applications.