In this paper we investigate the thermal insulation efficiency of a novel concept of panelized wall system for non-residential buildings made of aluminium and polyvinyl chloride (PVC). The study is carried out by combining the results of 2D Finite Element Method (FEM) thermal and fluid dynamics numerical simulations, experimental data and theoretical investigations. According to the simulation results, technological aspects, theoretical and experimental data, we found a good thermal efficiency characterization of the double-chamber panels configuration. We theoretically investigate the thermal efficiency of the proposed system as a function of the distance between the panels and the wall to be insulated, finding that thermal insulation efficiency does not depend on the distance from the wall for gaps larger than about 3 cm. By combining the different approaches developed in this paper, we find a good agreement between theoretical, numerical and experimental results. This study demonstrates that the proposed methodology used to estimate and measure the heat transfer and the thermal efficiency, can be applied to different panels types made of different materials and in different configurations. The goal of the paper is to provide a guideline to model and to characterize the thermal isolation efficiency of panel.