Refrigeration applications find extensive use across engineering and medical sectors. With energy resources being limited and fossil fuels being predominant in electricity generation, reducing the environmental impact and energy consumption of refrigeration systems has become a prime concern for engineers and scientists in recent years. This chapter conducts energy and exergy analyses of a modified two-phase ejector-enhanced cascade refrigeration (MECR) cycle for low-temperature applications and compares its performance with that of the conventional two-phase ejector-enhanced auto-cascade refrigeration (EACR) cycle. The MECR cycle consists of a high-temperature cycle with an R23/R134a binary refrigerant mixture and a low-temperature cycle with an R170/R290 binary refrigerant mixture. In the MECR cycle operating with an evaporation temperature of −60 °C and a condensation temperature of 35 °C, the coefficient of performance (COP) is 0.50, with an exergy efficiency of 16.8%. When compared with the EACR cycle operating with R170/R290, the COP and exergy efficiency of the MECR cycle increased by 35.1% while the total compressor work and total exergy destruction rate decreased by 26.0% and 29.7%, respectively. Notably, the volumetric cooling effect increased by 612.2%.