Global warming is one of the most dangerous ecological issues facing the globe. Refrigerants are a major contributor to global warming. This investigation mainly focuses on the analysis of a greener nanorefrigerant. Nanorefrigerant can improve the efficiency of refrigeration and air conditioning systems that use vapor compression. In the present investigation, mathematical and computational methods are used to assess the heat transfer and pressure drop properties of TiO2/R1234yf. In order to analyze the heat transfer characteristics and the transport features of the innovative nanorefrigerant, appropriate mathematical predictive models were adapted from earlier investigations. The models are validated by the experiments using TiO2/POE nanolubricant as a test fluid. The investigation was conducted with a temperature range of 10 °C to 40 °C and a volume percentage of nano-sized TiO2 particles in R1234yf refrigerant ranging from 0.2 to 1%. According to the research, the introduction of nanoparticles increases viscosity, thermal conductivity, and density. However, as the amount of nanoparticles rises, the specific heat capacity of the nano-enhanced refrigerant decreases. The nanorefrigerant’s heat transfer coefficient and pressure drop are improved by 134.03% and 80.77%, respectively. The outcomes observed from the predictive technique and the simulation approach had an average absolute variation of 9.91%.