South Asia is the subregion of Asia with the most neighbors of China. Although the high mountains in the Great Himalayas spatially separate South Asia from East Asia along the border of China’s autonomous region of Tibet, the geographical items such as mountains and rivers link the countries in South Asia with China, resulting in a special and complex geopolitical environment and relationship. In this geopolitical relationship, the transboundary rivers are becoming a key issue of this region in an era of increasing water stress. Depleted and degraded transboundary water supplies have the potential to cause social unrest and spark conflict within and between countries in South Asia, and complicate the geopolitical relationship among them. In addition, the increasing impacts from climate change and human activities will definitely bring many transboundary eco-environmental issues in this region, projecting a big challenge to regional stability and development. The key issues related to the water resources supplement and exploration require the transboundary rivers to be a positive role in regional water resources utility and exploration, and the result will definitely affect regional relationship and water security. How to handle these issues and challenges will be a question for the countries in this region with a long time. Currently, the “Belt and Road” Initiative represents an opportunity to build a shared vision for common prosperity through regional cooperation and is a way to inject new positive energy into world peace and development. In the light of this, the countries with transboundary rivers in South Asia must come together to construct a cooperative mechanism of water security, and adopt a win-win cooperation for the use of transboundary rivers under the principles of “equal”, “equitable” and “reasonable”.