We integrate equilibrium and rate-based models to formulate a hybrid optimization scheme for designing an ionic liquid-based extractive distillation process for mixed-refrigerant separation. The equilibrium model assumes vapor–liquid equilibrium at each stage but challenges arise with low-volatility, high-viscosity solvents, which drive the system away from equilibrium. The rate-based approach considers mass and heat transfer rates, giving more accurate representation. We compare the two models for separating R-410A, an azeotropic mixture of R-32 and R-125, using [EMIM][SCN] ionic liquid as entrainer. Analyzing over 4300 simulations with various dimensionality reduction and topological analysis techniques, we find that predictions from the two models exhibit similar trends, but the overestimation in equilibrium-based purities sometimes leads to infeasible process designs. The proposed optimization algorithm thus combines the strengths of the two models to locate feasible and optimal designs.