The growing demand for telemedicine services, accelerated by the COVID-19 pandemic and new normal, has highlighted the critical roles of entrepreneurial ecosystems in fostering innovation, improving healthcare access, and promising sustainability of digital health ventures. This study systematically reviews the entrepreneurial ecosystem in telemedicine healthcare businesses, focusing on the elements and roles contributing to their success. This study introduces a novel comprehensive framework of the entrepreneurial ecosystem in telemedicine, addressing gaps in previous research that focused narrowly on technological, demographic, or operational aspects, thereby providing a holistic understanding of how these factors collectively drive innovation and sustainability in telemedicine healthcare businesses. A comprehensive review of literature from the Scopus database was conducted by applying the PRISMA protocols and the Gioia method. Based on the research findings, this review proposes the 4Ps fishbone conceptual framework of the entrepreneurial ecosystem that drives success in telemedicine healthcare businesses. This review identified key elements of the entrepreneurial ecosystem, such as formal institutions, entrepreneurship culture, and networks that significantly influence the growth and sustainability of telemedicine ventures. The prominent roles of the entrepreneurial ecosystem in the telemedicine health service business include people development, process optimization, policy framework, and platform advancement. This study highlights how the entrepreneurial ecosystem drives success in telemedicine healthcare businesses, providing strategic insights for entrepreneurship, practical guidance for managers, and policy recommendations to foster growth.