The paper analyzes the distribution pattern of resources, ecological environment, society and economy, and holds that it is conducive to Silk Road countries to carry out Omni-directional and multi-level economic cooperation. Then the article puts forth main modes and paths of sustainable economic development for the Silk Road Economic Belt (SREB): ecological civilization mode, regional economic integration mode, transportation economic belt mode and international tourism economic zone mode. Finally, the article summarizes the key scientific issues for the sustainable development in the SREB and puts forward several action projects which include establishing International Scientists League and Think Tanks, establishing international information sharing platform and scientific policy-making system of ecological environment and sustainable development of the SREB, starting international science cooperation and technology traineeship program of the SREB, founding the international cooperation committee in the SREB and founding transnational construction and win-win cooperation mechanism of coping with climate change and ecological environment.