This study examines the feasibility of utilizing mixed-oxide fuel [(U0.9, rgPu0.1) O2] instead of traditional UO2 in nuclear reactors. The utilization of (U0.9, rgPu0.1) O2 is particularly significant as it represents an effective approach to nuclear fuel recycling by combining reactor-grade plutonium extracted from partially used nuclear fuel and depleted uranium obtained through the enrichment process. The fundamental neutronic characteristics, such as the radial power distribution, were investigated using the MCNPX 2.7 algorithm to identify the specific channel for subsequent thermal-hydraulic (TH) analysis. The TH analysis was conducted using COMSOL-Multiphysics, allowing for the estimation of the fuel rod’s axial and radial temperature profiles, as well as the determination of the departure from the nucleate boiling ratio. Furthermore, the coupling between heat transfer and solid structure (SS) was achieved using the Multiphysics tool in COMSOL-Multiphysics. This coupling facilitated the simulation of key SS parameters, including von Mises stress, volumetric strain, and displacement, while considering the influence of heat transfer. The results demonstrate significant improvements and enhanced safety margins when utilizing (U0.9, rgPu0.1) O2.