This chapter focuses on the different issues, challenges, new opportunities, and potential risks related to the collaborative model of international higher education. To provide clarity on the different types and levels of these issues, three categories are used for analysis. The first micro-level category focuses on operational issues at the institutional level and includes funding, quality assurance, and accreditation, double and joint degrees, collaborative and interdisciplinary applied research, cross-cultural tensions, and recruitment and retention of academic staff. The meso-level analysis addresses more strategic kinds of issues such as changing rationales and priorities, establishment of satellite education centers, impact of online learning, governance, national policies and regulations, visas and immigration. The macro level addresses the often-ignored political issues related to relations between and among the collaborating countries/partners as well as the wider global geopolitical implications. Two fundamentally different approaches—the knowledge diplomacy approach and the knowledge for soft power approach—to the role of international higher education, research, and innovation in international relations are elaborated on. The differences between the two approaches, including the role of values, self-interests, strategies, and outcomes, are discussed. A brief discussion on the potential impact that geopolitical relations at the global level can also have on international collaborative higher education institutions ends the book along with a plea for more interdisciplinary research on the collaborative model on international higher education institutions.