Research on entrepreneurial ecosystems has largely taken a macro-perspective to better conceptualize and map the determinants and evolution of entrepreneurial ecosystems, yet has neglected the micro-level interactions of various entrepreneurial ecosystem actors. Recent criticisms of entrepreneurial ecosystems have centered on the lack of explicit case and effect relationships, attribution, units of analysis, the different use of network definitions as well as the static nature of existing frameworks. The purpose of our paper is to present a micro level principal investigator (PI)-centered governance framework that addresses these posited criticisms and in doing so identifies the value creation indicators (benefits), PI capabilities, the problem categories (costs), and solving mechanisms that PIs can use to govern effectively and efficiently large-scale publicly funded research programs. In leading such research programs, PIs interact with different actors within entrepreneurial ecosystems and manage governance issues, conflicts, and tensions effectively at the micro level to deliver the anticipated benefits and costs for each actor. Our framework provides the basis for future empirical research on entrepreneurial ecosystem as we have attributed cause and effect at an individual actor level and conceptualized the governance challenges at a micro rather than at the macro level that overcomes the static nature of previous frameworks.