To fulfill the requirement of multi-refrigeration temperature, multi-target-temperature techniques are increasing research interests for industrial and commercial applications. Taking forward the previous research keeping in mind the electric power saving, a novel vapor compression-absorption multi-target-temperature cascade (VCAMTTS) system is proposed, in which NH3-H2O pair is used as vapor absorption section in the high-temperature circuit whereas two out of three refrigerant R717, R410A, and R134a are used in two lower circuits results in three possible configurations as NH3-H2O/R717 + R410A, NH3-H2O/R410A + R134a, and NH3-H2O/R134a + R717. This detailed analysis is based on the selection of the best configuration, investigating these on every aspect of energy, exergy, and economy (EEE). The whole investigation revolves around the parameters such as coefficient of performance (COP), exergy efficiency, and their sensitivity due to change of evaporator temperature and refrigerating capacity distribution ratio, exergy-economic factor, and product cost rate. Based on its best thermodynamic and thermal-economic performance, NH3-H2O/R410A + R134a (NHRARa) system can be a better option for multi-target-temperature refrigeration applications. Further, from the thermoeconomic analysis the optimum COP, exergy efficiency, and minimum cost obtained are about 0.3378, 8.29%, and 24.19 $/h, respectively.