Entrepreneurial actions can have superior performance when originated inside structured innovation ecosystems. New organization models of collaboration between different types of innovation ecosystem can increase the likelihood of successful business and impact creation. This requires the development of new ways of collaboration, from both the academic and the company’s point of view. This chapter analyses the method of supporting entrepreneurship of two innovation ecosystems that are enabled by the use of exponential technologies, such as information and communication technology (ICT). The main findings observed during the long-term collaboration of the two innovation ecosystems extend the field of entrepreneurship and innovation. Further research could measure the drivers of success of the ecosystems in the generation of new ventures coming from academia, as well as the high impact of these ventures on the target markets. Finally, this chapter presents practical implications for entrepreneurs of knowledge-based start-ups, as well as the leaders of innovation ecosystems.