This study investigates the multi-objective optimization and 4E (energy, exergy, economy, environmental impact) analysis of a triple cascade refrigeration system (TCRS) equipped with hydrocarbon refrigerants (1-butene/Heptane/m-Xylene) for ultra-low temperature applications. The system is designed for applications such as vaccine storage, quick-freezing, frozen food preservation, cryogenic processes, and gas liquefaction. The research integrates conventional thermodynamic analysis with economic and environmental impact assessments, and employs multi-objective optimization (MOO) to determine optimal operating conditions. The study investigates the effects of evaporator temperature, condenser temperature, Lower Temperature Circuit (LTC) condenser temperature, Mid Temperature Circuit (MTC) condenser temperature, and Cascade Condenser temperature difference on three objective functions: COP, exergy efficiency, and overall plant cost. Quadratic equations for these objective functions are generated using the Box-Behnken method, and MOO is performed using the genetic algorithm to maximize COP and exergy efficiency while minimizing the overall cost rate. Decision-making techniques TOPSIS and LINMAP are used to select a unique solution from the Pareto Front. The results show that for a 10-kW capacity TCRS, the optimal operating conditions are T_evap = −101.023 °C, T_cond = 36.545 °C, T_LTC = −69.047 °C, and T_MTC = −34.651 °C, with COP = 0.71, exergy efficiency = 0.51, and total plant cost = 38,262.05 S/year. Exergy analysis identifies the HTC compressor and throttle valve as key contributors to exergy destruction, while economic analysis highlights capital and maintenance costs as primary contributors to the overall cost.This study investigates the multi-objective optimization and 4E (energy, exergy, economy, environmental impact) analysis of a triple cascade refrigeration system (TCRS) equipped with hydrocarbon refrigerants (1-butene/Heptane/m-Xylene) for ultra-low temperature applications. The system is designed for applications such as vaccine storage, quick-freezing, frozen food preservation, cryogenic processes, and gas liquefaction. The research integrates conventional thermodynamic analysis with economic and environmental impact assessments, and employs multi-objective optimization (MOO) to determine optimal operating conditions. The study investigates the effects of evaporator temperature, condenser temperature, Lower Temperature Circuit (LTC) condenser temperature, Mid Temperature Circuit (MTC) condenser temperature, and Cascade Condenser temperature difference on three objective functions: COP, exergy efficiency, and overall plant cost. Quadratic equations for these objective functions are generated using the Box-Behnken method, and MOO is performed using the genetic algorithm to maximize COP and exergy efficiency while minimizing the overall cost rate. Decision-making techniques TOPSIS and LINMAP are used to select a unique solution from the Pareto Front. The results show that for a 10-kW capacity TCRS, the optimal operating conditions are T_evap = −101.023 °C, T_cond = 36.545 °C, T_LTC = −69.047 °C, and T_MTC = −34.651 °C, with COP = 0.71, exergy efficiency = 0.51, and total plant cost = 38,262.05 S/year. Exergy analysis identifies the HTC compressor and throttle valve as key contributors to exergy destruction, while economic analysis highlights capital and maintenance costs as primary contributors to the overall cost.