The rapid integration of data-driven healthcare services with medical informatics is reshaping entrepreneurship in the healthcare sector. Yet, there is limited understanding of the internal and external factors that drive success in this area. This study aims to identify the development of global literature on internal and external factors that are key to the success of implementing medical information for data-driven entrepreneurship in the healthcare business. Unlike previous studies, this research systematically integrates internal and external factors to establish a comprehensive framework for data-driven success in healthcare entrepreneurship through medical informatics. Using the Systematic Literature Review (SLR) method, peer-reviewed papers published were analyzed from the Scopus database, focusing on medical informatics and entrepreneurship. The findings reveal four key internal success factors: data-driven capabilities, digital transformation leadership, a dynamic collaborative ecosystem, and a driven entrepreneurial spirit. Four external factors were identified: directive and resource environment, competitive dynamics, policy support, and digital training integration. Based on the research findings, this study proposes the 8D padlock conceptual framework as the key success factor of medical informatics for data-driven entrepreneurship in the health business. These results highlight the importance of enhancing data-driven capabilities, supporting digital transformation, fostering collaboration, and ensuring continuous investment in digital training. Policymakers and entrepreneurs can use these insights to create more sustainable and innovative healthcare ventures.