<p>Given the high cost and time demands associated with experimental thermodynamic measurements, the development of reliable, theory-based equations of state (EOSs) is crucial for the accurate prediction of refrigerant behavior in practical thermal systems. Such predictive capabilities are essential for optimizing the design, efficiency, and energy performance of refrigeration and heat pump technologies. In this study, a novel two-parameter cubic EOS was developed within a simplified statistical mechanical perturbation theory framework. The temperature-dependent parameters of the proposed model were optimized using saturated property data for 35 refrigerants, covering a wide range of industrially relevant compounds including chlorofluorocarbons, hydrochlorofluorocarbons, hydrofluorocarbons, hydrocarbons, and natural inorganic refrigerants. Comparative evaluations were conducted for vapor–liquid equilibrium (VLE), saturated and high-pressure liquid densities, normal boiling points, enthalpies of vaporization, pressure–enthalpy (P–H) diagrams, pressure–pressure (P–S) diagrams, isochoric specific heat capacities (<i>C</i>_<i>v</i>), isobaric specific heat capacities (<i>C</i>_<i>p</i>), speed of sound (<i>u</i>), and the coefficient of performance for selected refrigerants, employing the proposed EOS alongside other widely adopted two-parameter models. Furthermore, the new EOS was applied to mixture systems, including isothermal VLE calculations for azeotropic and non-azeotropic binary mixtures, liquid density predictions, thereby demonstrating its versatility and applicability to chemical and process engineering refrigerant systems. The results of the comparative analyses consistently highlight the superior predictive performance of the proposed simple cubic EOS relative to commonly used existing models.</p>