Innovation, sustainability, and collaboration are all related in their efforts to manage multiple dimensions of organizational and institutional policies and practices. This chapter conceptualizes an integrative Sustainability Science perspective of innovation, sustainability and collaboration, providing and overview of the three topics and their relative importance to overall advancement of Global Sustainability, in particular through innovations from the South. It is argued that Cross-border collaboration (North-south and South-South), is necessary to achieve this goal and various collaborative arrangements and stakeholders in these arrangements are discussed. Our perspective emphasizes not only of the need but also the challenges of sustainability-oriented projects involving cross-borders partnerships. The chapter finally introduces and discusses the various remaining chapters in this book and presents summaries, insights and linkages amongst these chapters.