Natural science museum is defined as a socially-involved institution dedicating itself to science communication and education. The development of natural science museum is currently faced with fresh challenges and opportunities largely due to the overall trend of world multi-polarization, economic globalization, cultural diversity, and information booming. By starting with an analysis of the development of natural science museums, globalization and sustainable development, uneven regional development and the major influence of technology and social interaction as socio-contextual factors are analyzed in this paper. According to the analysis, it is analyzing that “the Belt and Road” Initiative has provided a key platform and a package of solutions for natural science museums in terms of coping with the above-mentioned challenges. Therefore, as proposed in this paper, the following suggestions should be taken into account: strengthen the communication and cooperation among natural science museums; build a platform for scientific communication; promote the activities and events related to exhibitions and educational programs; provide a range of professional training programs to build leadership; establish mutual benefits& sharing mechanism; as well as promote a further development in science and technology, education and culture in the countries and regions along “the Belt and Road”.