Abstract: The article introduces the latest development in Greater Mekong Subregion (GMS) economic cooperation program and analyzes issues, challenges, opportunities, major cooperation areas and policy measures in the cooperation. Promotion of GMS economic cooperation and development needs summit consultation, active encouraging private investment, improving investment environment, and formulating principles for handling conflict of interests in facing enormous challenges like poverty, labor quality, infrastructure, eco-environment, infectious diseases, lacking of macro strategies, and risks from globalization and regionalization. Realization of China’s national interests in the cooperation comes from strengthening China’s cooperation with countries in the region in people’s livelihood, education, and science and technology, building comprehensive development and growth poles along the borders, and promoting the internationalization of RMB through regional cooperation.