The transmission thermal losses in opaque envelope components are influenced by mass transportation phenomena, that depend on the built-in humidity level, material hygrometric properties and climatic conditions. Moreover, latent heat exchanges due to wetting and drying processes, promoted by rainfall, incident solar radiation, velocity and wind direction, must be also considered. As a consequence, identical opaque walls offer different transmission losses as a function of exposition, time and location. Through the dynamic procedure of the EN ISO 15026, implemented in the WUFI software, and considering two opposite climatic conditions of the Mediterranean area, the combined effects of heat and mass transfer have allowed for determining dynamic thermal transmittance (U-value) of three different wall solutions. By referring to the steady U-value, deviances up to 15% were detected for walls North facing. A novel approach developed to employ WUFI results in the TRNSYS environment was employed for determining how the variable U-values affect the heating demand of a reference building, obatining increases of 5–9% at a seasonal level.