Higher education institutions (HEIs) must strategically participate in research, innovation, and entrepreneurship (RIE) to maintain relevance, competitiveness, and efficacy in an increasingly knowledge-driven global economy. This chapter looks at both strategic frameworks and practical ways to make research, innovation, and entrepreneurship (RIE) a part of the main goals of academic institutions. It examines institutional frameworks, case studies, and policy recommendations across several global regions. The chapter provides important information on how to create research cultures that are productive, how to encourage interdisciplinary innovation, how to incorporate entrepreneurial thinking in curricula, and how to create ecosystems that support the commercialization of knowledge and the creation of new startups and successful businesses.