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The use of nanoparticle-infused blended refrigerants is essential for achieving an effective sustainable system. This investigation analyses the efficiency of three nano-refrigerants (CuO-R152a, TiO2-R152a and TiO2-R113a) on the basis of the thermal performance and energy usage of the compressor using MATLAB-Simulink in the vapour compression refrigeration cycle with a two-phase flow domain. Also, nanoparticle volume concentrations of 0.1%–0.5% in the basic refrigerants are investigated. In the Simulink model, the outcomes are calculated mathematically. Using the NIST chemistry webbook, the thermo-physical characteristics of base refrigerants were calculated, and different numerical models were used to compute the characteristics of nano-enhanced refrigerants. MS Excel was used to perform the liquid–vapour interpolation. It was discovered that refrigerants with nanoparticles have superior heat-transfer properties and operate most excellently at an optimal volume fraction of 0.1% for TiO2-R152a and CuO-R152a with a coefficient of performance (COP) as 10.8. However, the other blended nano-refrigerant TiO2-R113a performed the best at 0.5% of nano-particle volume fraction with a COP value of 5.27. [ABSTRACT FROM AUTHOR]