Current literature validates the magnitude of physician burnout as a complex challenge affecting physicians, patients, and healthcare delivery that mandates science-informed intervention. Physician burnout affects both individual practitioners and patient care delivery. Interventions, defined as roadmaps, to prioritizing and supporting personal wellbeing encompass organizational, individual, and moral injury, with virtually no consensus on optimal approaches. The purpose of this conceptual review is to present evidence-based innovative insights on contributing factors, mitigation, and designing adaptive systems to combat and prevent burnout. Science-informed policy initiatives that support long-term organizational changes endorsed by both leadership and institutional stakeholders are keys to sustaining personal wellbeing and ending burnout.