Ethiopia is implementing a ten-year perspective plan (TYPP 2021-2030) with multi-layered activities that would enhance the capacity of the nation in science, technology, and innovation and effective application to economic transformation. While the country is endowed with many untapped natural resources and opportunities in using different areas of science and technology for development, its socio-economic development is not satisfactory. The current Ethiopian government as a part of its multi-layered activities in the TYPP has recently decided and launched a nuclear power program (NPP) to use nuclear science and technology applications in its energy mix and sustainable development strategies and is preparing infrastructures for its effective implementation. This paper provides a review of the role of nuclear science and technology in energy production and sustainable development; and analyses the status, challenges, and issues in the Ethiopian national nuclear program. The review sets out to discuss the main issues in a national nuclear program, nuclear energy management, and nuclear knowledge management demands and strategies for its effective application. Knowledgeable commitment to the nuclear science and technology program in developing countries like Ethiopia can boost economic growth.