Science diplomacy is a new field connecting academic and diplomatic communities to address and elaborate on global and regional issues and challenges. The concept of Global South has become a popular topic in international relations and comparative and international education, particularly in the context of North and South relations, which are commonly regarded as the relationship between developed and developing countries. In this direction, cultural and political factors can change and impact how science related areas are perceived and valued in different countries and regions. Through examining scholarly literature, this chapter argues that effective science diplomacy and networking in the Global South require a deep understanding of the local context, including political, cultural, and educational factors that may affect scientific research and engagement with diverse stakeholders of the issue. Overall, this chapter concludes that more effective and inclusive collaborations that benefit both local communities and global community can be promoted by acknowledging these factors.