Entrepreneurial ecosystems have developed from a powerful idea and concept into a transdisciplinary research program, increasing our understanding into entrepreneurship-led development and providing actionable knowledge for improving the conditions for entrepreneurship and development. In this paper we take stock of the progress to date and synthesize the findings of 181 empirical scientific entrepreneurial ecosystem studies with a systematic literature review. We organized the review around five key mechanisms that explain the nature and development of entrepreneurial ecosystems: (1) interdependence of its elements, (2) upward causation explaining entrepreneurial ecosystem outputs and (3) outcomes, (4) downward causation and path dependence, and (5) inter-ecosystem links. We summarize the findings and outline opportunities for research and discuss policy implications in the light of a transdisciplinary entrepreneurial ecosystem research program. This paper is of interest for scholars of all academic disciplines that provide knowledge that is relevant for the understanding of entrepreneurial ecosystems, entrepreneurship and entrepreneurship-led development, but also for all stakeholders involved in the development of entrepreneurial ecosystems.