This work presents the optimization of a two stage cascade refrigeration system (TS CRS), based on exergetic, economic, environmental, and sensitive analysis (3ES). R134a and R744 are considered as the refrigerants of high and low temperature circuits, respectively. Two single optimization strategies including exergetic and economic optimizations and a multi objective optimization are applied on the problem. In the first step, a comprehensive performance evaluation of different effective parameters, based on the genetic algorithm, used to indicate the optimum operative conditions in single objective strategies. In the next step, a multi objective optimization is performed with considering a decision making strategy based on the Pareto frontier using TOPSIS method. The higher exergetic efficiency and lower cost found in the exergetic and economic single optimization, respectively. The multi objective optimization results demonstrate that, the total system cost and the exergetic efficiency increase 28.6% and 99.5%, respectively, compared to the base design, and 46.6% higher energy can be saved in the compressors.