<p>The global healthcare system is confronting significant structural challenges and urgently requires innovative solutions. Academic entrepreneurship has emerged as a critical response by translating medical discoveries into practical solutions. While research on academic entrepreneurship in healthcare is rapidly growing, the existing literature remains fragmented and lacks a comprehensive synthesis of its progress and future directions. This review addresses this gap by conducting a framework-based systematic literature review of 85 peer-reviewed articles sourced from Scopus and Web of Science. Guided by the SPAR-4-SLR protocol, the review employs two organizing frameworks. The antecedents-phenomenon-consequences (APC) framework uncovers the enabling and constraining factors,diverse entrepreneurial pathways, and both the positive and negative effects associated with academic entrepreneurship in healthcare. Complementing this, the theory-context-method (TCM) framework provides structured insights into the theoretical foundations, research contexts, and methodological strategies applied in the field. Additionally, the review identifies the major gaps in the existing literature and offers a few recommendations for future investigation on academic entrepreneurship in healthcare across three key dimensions: new theoretical perspectives, expanded research settings, and diversified methodological approaches. By integrating these perspectives, the study offers a synthesized understanding of existing research, identifies critical knowledge gaps, and provides actionable insights for scholars, institutional leaders, and policy stakeholders committed to advancing academic entrepreneurship in healthcare.</p>