An attempt has been made to investigate numerically a two-stage refrigeration system with flash intercooler of 50 kW cooling capacity using refrigerant R410A and its possible alternative R32. Development of the simulation model for the analysis of the system has been carried out in engineering equation solver considering the energetic, exergetic, economic, and environmental aspects. Evaporator and condenser temperatures have been varied from −50 °C to −25 °C and 40 °C to 55 °C, respectively, to carry out the simulation work. Co-efficient of performance (COP), exergetic efficiency, and plant cost rate are the three performance parameters computed in this present work. Results show that the performances of the system using R32 are comparable with those of the system using R410A. It is also observed that R32 shows slightly better thermo-economic performances at higher condenser temperature. Multi-objective optimization has also been carried out using the toolbox available for optimization in matlab to obtain the optimum performance and optimum operating conditions for both the refrigerants. Optimization results also show better thermo-economic performances of R32 over R410A though compressor discharge temperature is higher in case of R32.