Plastic materials are increasingly becoming used in the building envelope, despite a lack of investigation on their effects. In this work, an extruded Acrylonitrile-Butadiene-Styrene panel has been tested as a second-skin layer in a ventilated facade system using a full-scale facility. The experimental results show that it is possible to achieve performances very similar to conventional materials. A numerical model has then been developed and used to investigate the performances of plastic and composite polymer panels as second-skin layers. The experimental data has been used to verify the behavior of the numerical model, from a thermal point of view, showing good reliability, with a root mean square error lower than 0.40 °C. This model has then been applied in different refurbishment cases upon varying: the polymer and the manufacturing technology (extruded or 3D-printed panels). Eight refurbishment case studies have been carried out on a typical office building located in Napoli (Italy), by means of a dynamic simulation software. The simulation results show that the proposed actions allow the reduction of the thermal and cooling energy demand (up to 6.9% and 3.1%, respectively), as well as the non-renewable primary energy consumption (up to 2.6%), in comparison to the reference case study.