Abstract: Molybdenum-rhenium (Mo-Re) alloys are promising candidates for structural materials of advanced nuclear reactors, endowing with high melting point, good strength and plasticity, outstanding compatibilities with nuclear fuels and alkali metal coolant. The strategic incorporation of Re proves critical for improving the inherent room-temperature brittleness of pure Mo metal. However, the effects of Re doping show significant dependence on Re contents, and long-term irradiation will induce obvious hardening of Mo-Re alloys. Therefore, it is necessary to understand the high-temperature mechanical properties of Mo-mRe alloys (m=3%, 5%, 10%, 14%) with varying Re compositions. Nano-indentation technology has become an important tool to characterize the hardness change of materials after irradiation, because the indentation depth is similar to the thickness of the damage layer caused by ion irradiation. Therefore, in the present study, the nano-indentation load-displacement curves of Mo-mRe were simulated at different temperatures by molecular dynamics (MD) methods, based on which the nano-indentation hardness could be derived. To understand the effect of irradiation on nano-indentation hardness, displacement cascade at different temperatures were calculated, and the Frenkel defects surviving after the cascade were analyzed. The nano-indentation behaviors for Mo-mRe after displacement cascade were then investigated to evaluate the changes in the nano-indentation hardness due to the introduction of irradiation defects. The results show that the nano-indentation load of Mo-mRe decreases with both the increase of Re contents and temperatures. The uniformly distributed solute Re atoms will decrease the migration barrier of dislocation line, thus enhancing the deformation of Mo-Re alloy. High temperature also promotes the mobility of dislocation and shows a softening effect on Mo-Re alloy. The Frenkel defect pair numbers surviving after the equilibrium stage of displacement cascade decrease at high temperature, due to the enhanced diffusion and recombination of defects. However, at high temperature, Re contents exhibit complex influences on the survival Frenkel defect pair numbers. As the Re content increases, displaced Re atoms combine with Mo atoms to form more mixed Mo-Re interstitial pairs, predominantly existing as a single Mo-Re dumbbell. This leads to an overall reduction in the clustering of interstitial atoms in Mo-Re with high Re contents. For Mo-Re alloys subjected to displacement cascade, the increase in nano-indentation hardness for low-Re-content alloys (Mo-3Re, Mo-5Re, and Mo-10Re) under 650 °C shows significant enhancement, while the increase in nano-indentation hardness for Mo-14Re is the lowest. Based on the findings, temperature and Re content exhibit a dual influence on the nano-indentation mechanical response of Mo-Re alloys. Increasing Re contents within a certain range can help enhance the high-temperature mechanical properties of Mo-Re alloys to some extent.