Abstract: Irradiation damage of fuel cladding materials is the critical bottleneck limiting the safe, long-term operation of advanced high-temperature nuclear reactors. Molybdenum-rhenium (Mo-Re) alloys, with outstanding high-temperature strength, thermal conductivity and neutron irradiation resistance, are leading candidate cladding materials for next-generation fast reactors and space nuclear reactors. However, their complex microstructural evolution under irradiation—especially the coupled effects of irradiation defects and ballistic mixing on precipitate stability, remains poorly understood. Existing phase-field models overlook the synergy between defect accumulation and atomic mixing, causing large deviations between simulations and experiments. This work develops a comprehensive phase-field model integrating irradiation-induced vacancies and ballistic mixing, to systematically study microstructural evolution of Mo-Re alloys with varying Re content at different temperatures. A robust phase-field model was constructed for Mo-Re binary alloys, with total free energy comprising chemical, gradient and irradiation-induced contributions. Order parameter evolution follows the Allen-Cahn equation, and solute diffusion follows the Cahn-Hilliard equation. A Gaussian-distribution ballistic mixing term was introduced to describe atomic relocation from displacement cascades, and irradiation-induced vacancy accumulation was incorporated to modify the free energy of the BCC matrix. Thermodynamic parameters for BCC, χ and σ phases were adopted from an optimized database; Free energy curves were calculated via Pandat and polynomial fitted for efficiency. Governing equations were numerically solved by the finite difference method. Simulations explored the effects of temperature (673-1 573 K), Re content (5%-41%, in terms of atomic fractions) on precipitate nucleation, growth and stability, validated against literature experimental data. Simulation results show temperature dominates precipitate stability in irradiated Mo-Re alloys. At high temperatures, enhanced thermal diffusion and ballistic mixing accelerate χ and σ phases’ dissolution, with faster dissolution at lower Re content. Irradiation-induced vacancies significantly promote low-temperature precipitation by elevating BCC matrix free energy and increasing thermodynamic driving force for Re segregation—stable χ phase precipitates even in Mo-5Re at 873 K under irradiation, impossible without defects. With rising Re content, χ and σ phases compete for matrix Re: χ phase grows anisotropically as laths along the matrix 110 direction, while σ phase forms equiaxed particles. Simulated χ phase volume fractions (12.29% for Mo-5Re, 18.90% for Mo-10Re) agree well with experimental data (15.53% and 17.2%), with error <10%. This study reproduces the irradiation-induced microstructural evolution of Mo-Re alloys and clarifies the synergistic regulation of temperature, irradiation and composition on precipitate stability. Ballistic mixing drives microstructural evolution via homogenization and precipitate dissolution, while irradiation vacancies dominate Re-rich phase precipitation. The phase-field model enables quantitative prediction of irradiation-induced microstructural changes, laying a theoretical foundation for understanding irradiation hardening and embrittlement, and guiding composition optimization, performance enhancement and service life evaluation of advanced nuclear fuel cladding.