Nowadays, advanced hygrothermal simulation tools are available and they are widely used to predict moisture-related risks in building components, such as mold growth and increased conductive heat losses. This paper takes advantage of these capabilities to analyze moisture-related risks in the innovative wood-based retrofit solutions, developed in the ongoing H2020 “e-SAFE” project. In particular, simulations carried out through the Delphin software for the warm Mediterranean climate of Catania (Italy) allowed assessing the effectiveness of several insulating materials used in the wall assembly and the moisture-related performance determined by adopting either a waterproof membrane or a vapor barrier in convenient positions. The results show that the solutions with highly permeable and highly moisture-capacitive insulation (e.g., wood fiber) are mold free, but at the expense of increased heat losses by up to 12%, compared to dry materials). In some circumstances, foam glass or extruded polyurethane could be preferable, due to their high resistance to mold growth and their flat sorption curve. The vapor-open waterproof membrane applied to the outer side of the insulation is suggested, while a vapor barrier on the outer side of the existing wall worsens mold-related issues.