Prefabricated buildings are increasingly popular worldwide, driven by technological advancements and the demand for sustainable and energy-efficient construction. However, the thermal performance of typical multi-layered and compacted prefabricated wall panels remains uncertain, leading to overdesigned HVAC and building envelope systems. This results in higher utility bills, unnecessary expenses, and increased material, labor, and transportation costs. While experimental analysis and computational simulations have proven effective for measuring the thermal performance of on-site wall panels (e.g., precast concrete, masonry), their effectiveness for exterior insulation finishing system (EIFS) prefab wall panels is unclear. This study aims to test the hypothesis that both experimental and computational analyses accurately measure the thermal performance of EIFS prefab wall panels under various climate conditions and yield to similar results. To achieve this, (1) experimental test analysis was conducted in an environmental chamber based on ASTM C1363 and ISO 8990 standards, and (2) computational simulation was conducted by employing THERM® at hot (65 °C) and cold (−16 °C) climates. The results showed that the experimental thermal resistance exceeded the computational thermal resistance by about 17% across hot and cold climates. These thermal resistances were then incorporated into a typical hospital building prototype in the U.S. modeled by U.S. Department of Energy in EnergyPlus™, resulting in substantial cost savings of approximately $396,000 over a 20-year lifespan due to the thermal resistance variations between experimental and computational analyses. The savings were achieved through a reduction in construction costs, accurate HVAC system selection, and lower utility bills. This study contributes to the improvement of prefabricated building design and energy performance analysis, leading to potential cost reductions in HVAC and building envelope system overdesign.