Abstract: The presence of a metastable γ-phase in its microstructure confers excellent irradiation stability on the U-Mo alloy, making it a promising candidate for advanced nuclear fuel. However, as reactor operational requirements increase, so too do the demands on fuel performance. Irradiation experiments reveal that U-Mo fuel experiences significant irradiation swelling at high burnup levels and elevated temperatures, which compromises its suitability for high-burnup applications. Consequently, there is a need to investigate enhanced U-Mo alloy-based fuels by modifying their composition. One strategy involves incorporating a third alloying element into U-Mo series alloys to create ternary alloys. In ternary alloy systems, due to the extensive range of possible compositions, conducting individual experimental research on each is impractical. Therefore research method is conducted using a combination of theoretical calculations and experimental verification. So thermodynamic theoretical calculation methods were employed. Specifically, the Thermo-Calc software was utilized to simulate and calculate the isothermal sections of the U-Mo-Ru ternary alloy. Several representative compositions were chosen, and corresponding ternary alloy samples were produced via vacuum arc melting. These samples underwent characterization through phase structure and microstructure analysis, followed by a predictive assessment of their potential applications in reactor environments. The Materials-Studio software was utilized to calculate the Gibbs free energy difference between the α-phase and γ-phase of various U-Mo series ternary alloys, subsequently identifying the optimal system. Additionally, the MEPH-20 nuclear fuel database within Thermo-Calc was employed to generate isothermal section diagrams for the U-Mo-Ru ternary alloy system and certain other U-Mo series ternary alloy systems. These analyses were performed on the binary U-Mo system. This paper aims to enhance the stability of the γ-phase by incorporating Ru, thereby improving the performance of U-Mo fuel. Using non-consumable arc melting technology, three types of U-Mo-Ru alloys with varying compositions were prepared, and isothermal decomposition experiments were conducted over a specified period. The microstructure of the U-Mo-Ru alloys was analyzed using a metallographic microscope and an X-ray diffractometer. The results indicate that at 565 °C, the decomposition of the γ-phase is delayed. For the U-9Mo-1Ru alloy, both phase diagram calculations and experimental data demonstrate that the γ-phase remains stable at 565 °C. Consequently, it can be concluded that the stability of the γ-phase in U-Mo alloys is directly influenced by the concentrations of Mo and Ru. As these concentrations increase, the stability of the γ-phase improves. In future, the U-Mo-Ru alloy’s behaviors under operating condition in reactor will be tested by using. Next, the in-core behavior of the U-Mo-Ru alloy (such as swelling, fission gas release, microstructure, etc.) will be verified through post-irradiation examination of irradiated test specimens.