This chapter presents the conceptual consequences of tensions emerging when universities engage with actors in peripheral regions, via three core literatures (regional innovation coalitions, evolutionary economic geography, regional leadership). Universities may dominate regional innovation coalitions, and their strategic challenge is finding appropriate ways to coordinate and shape these many diverse actors towards common goals. Success in doing this delivered a transformative effect via effectuative entrepreneurial discovery processes within regional innovation coalitions. The notion of the university third mission may even be unhelpful by suggesting a commonality between university-based activities that are absent or indeed may in reality be conflicts and differences.