Abstract: Molybdenum-rhenium (Mo-Re) refractory alloys are promising structural materials for advanced nuclear energy systems because they combine a high melting point, good high-temperature strength and the beneficial Re effect on the ductility of Mo. Their irradiation hardening is closely related to the interaction among dislocations, irradiation-induced defects and local chemical redistribution. This work aims to clarify how Re segregation near typical defects changes the depinning behavior of an a/2〈111〉 edge dislocation and to provide an atomistic reference for separating the chemical contribution of segregation from the geometric resistance of a nanovoid. A coupled variable-composition semi-grand canonical Monte Carlo and molecular dynamics (MD) simulation method was used. Atomic models of a Mo-7.7% Re (by atomic fraction) alloy containing an edge dislocation, a ϕ2 nm void and a dislocation-void pair were constructed with controlled boundary conditions and identical loading paths. Near-equilibrium segregation configurations at selected temperatures were obtained by VC-SGC-MC sampling, and subsequent shear loading simulations were performed by MD simulation to compare the critical resolved shear stress of random solid-solution, dislocation-segregated, void-only and void-plus-segregation configurations. The simulations show that Re atoms preferentially enrich at defect regions. At 500 K, the local Re concentration rises to 17.3% in the compressive region of the dislocation core and to 21.8% in the first atomic layer of the void surface, and the segregation shell extends over a range of about 3 nm from the void surface. The dislocation Cottrell atmosphere forms a strong chemical pinning field: The critical resolved shear stress increases from 231.6 MPa in the random solid solution to about 1 300 MPa in the segregated state, followed by a sharp stress drop after depinning. Temperature weakens this effect because higher configurational entropy and thermal activation promote dissipation of the segregation atmosphere and lower the effective depinning barrier. For the dislocation-void interaction, the Re-enriched shell produces a pre-attraction stage before direct contact and increases the peak depinning stress from about 400 MPa for the void-only model to about 470 MPa for the segregated void model. Through a controlled-variable comparison, the additional contribution of the void-surface segregation shell is therefore estimated to be about 70 MPa, corresponding to an approximately 18% increase in the total depinning resistance under the presentϕ2 nm void condition. The VC-SGC-MC result represents a thermodynamic-equilibrium segregation approximation rather than the full non-equilibrium radiation-induced segregation process under a specific reactor dose rate, defect flux and temperature history. Nevertheless, it identifies the thermodynamic tendency of Re enrichment at dislocations and voids and quantifies how this enrichment can modify dislocation depinning. The conclusions indicate that chemical-structural coupling around irradiation defects should be included in multiscale assessments of Mo-Re alloy irradiation hardening, while the dependence on void size remains a necessary subject for future simulations.