Entrepreneurs create and appropriate value by designing a system of interconnected and interdependent activities that determine how they do business. These activity systems span beyond the individual firm and compose complex interconnected ecosystems. Current research focuses on how entrepreneurs design new activity systems but do not focus on how these changes create new entrepreneurial opportunities and for whom. In this paper we ask why some people but not others identify and exploit entrepreneurial opportunities following changes in an activity system. Based on Lachmann’s theory of capital we develop a theoretical framework for analyzing how changes in the structure of activities in terms of knowledge substitution affect the knowledge required to identify and exploit opportunities by focusing on the role of complementarities and multiple specificities of capital resources. The results have implications for our understanding of the endogenous nature of entrepreneurship and the coevolution of business model innovation and innovation ecosystems.