ABSTRACT A novel optimization strategy for a compression-absorption cascaded refrigeration system (CACRS) consisting of a single effect vapor absorption system (VARS) and vapor compression system (VCRS), which employs several absorbent solution-refrigerant-refrigerant pairs to consider the combination of absorbent solution-refrigerant in VARS and refrigerants in VCRS as an optimization variable, is successfully implemented using various evolutionary optimization techniques. This article analyzes three different absorbent solution-refrigerant in the VARS with eleven different refrigerants in the VCRS. A nonlinear objective function is formulated based on exergy and environmental analysis, which is minimized using 10 different evolutionary optimization techniques. The proposed novel strategy reduces the complexity of using optimization techniques to select the best optimum absorbent-refrigerant-refrigerant pair. Differential evolution with multi-population-based ensemble of mutation strategies determined the minimum total annual cost as 13,137.78 US$/year for (CaCl2-LiBr-LiNO3-)-H2O-R152a. Lower condenser temperature and higher temperature difference in the cascade-condenser resulted in a minimum value for the total annual cost.