Despite splendid success in its development, future of nuclear power in the Republic of Korea (the ROK) faces a number of challenges. Majority of the public believe nuclear power is not safe resulting in low public acceptance. No long-term solution has been found for the management and disposal of spent nuclear fuel (SNF). Developing new sites for construction of new nuclear power plants has become very difficult. Government policy for future development remains uncertain. The ROK is now the 5th largest user country of nuclear energy and also a nuclear exporter. Given the strategic importance of nuclear power in the country’s energy security planning in the ROK, policy makers need to develop long-term plan for the country’s fuel cycle systems taking into account various factors involved such as domestic politics, nonproliferation, international relations, and economics. In relation to this consideration, this study performs economic evaluation of future nuclear fuel cycle options based on Once-through of the ROK. Various factors of the future development in the ROK are also considered in the study including nuclear phase-out, continuous use of nuclear energy at varying growth rate, and the reunification of the Korean peninsula. A spreadsheet model is developed as part of the methodology of screening material flow and economic evaluation and results are discussed for policy planning for the ROK as well as for nuclear developing countries.