Nuclear energy is an important part of the future source of energy due to their higher energy density and lower emission of pollutants. However, the traditional research method of “trial-and-error” may result in higher costs and lower efficiency because of the radioactivity of the nuclear fuels. The idea of Materials Genome Initiative（MGI）are suitable for the research and development of nuclear fuels. Focused on the nuclear fuel element material, our research group developed a multi-component thermodynamic database of U and Pu by coupling the CALPHAD and the first-principle method. Based on the thermodynamic database, the thermodynamic models under irradiation were established and the phase transformations under irradiation were systematically investigated. The microstructure evolutions of solidification and aging were simulated by using the Phase-Field method. The present multi-scale and multi-component materials design method based on MGI can provide important information for the design of composition, microstructure controlling and property improvement of nuclear fuels.