Heat pumps demonstrate a higher efficiency compared to conventional heating methods, such as electrical heating or burning natural gas. However, the challenge in heat pump technology remains finding an ideal refrigerant that can satisfy the requirements of having a low GWP, thermal suitability, and high efficiency. Thus far, researchers have shown that zeotropic mixtures could have great potential in heat pumps due to their superior thermodynamic properties. While many theoretical studies highlight that utilizing the temperature glide in zeotropic mixtures can significantly increase the COP in heat pumps, modeling studies with experimental validation remain scarce. In this study, the optimization of a multi-source heat pump experimental facility designed to test various hydrocarbon mixtures across a wide range of source and sink temperature will be presented. A model of the heat pump facility was developed using TIL library components within Dymola, with fluid properties accessed via the TILMedia interface connected to the REFPROP library. Parametric studies were conducted with a variety of hydrocarbon refrigerant mixtures. The heat sink temperature is varied from 35 °C to 70 °C and the heat source temperature is varied from −10 °C to 50 °C. The temperature spread between the inlet and outlet of the heat sink and source is varied from 5 to 25 K. The Model-Fit was used to calibrate the sink/source heat exchangers models, improving the accuracy of our simulations. The main objective of the study is to use the simulations to identify a refrigerant mixture that results in a superior COP across the majority of operating points. Selected operating points for that refrigerant mixture were tested experimentally for direct model validation.