The reduction of energy use in the buildings is expected to be reached by fulfilling several requirements of the low- and nearly-zero energy buildings (nZEB) policy. The improvement of the energy performance of the building envelope and the service systems of the existing buildings offers great potential for energy savings as the annual replacement of the existing stock is only 1 to 2%. The efficient way to accomplish the purpose and global goals of the nZEB is to apply the integrated design process, development, and application of prefabricated insulation elements on a large scale. In this project, in the Berlin area of Germany, prefabricated timber frame insulation elements were designed for the external insulation of the envelope of the apartment building in the serial renovation process, with the thermal transmittance of the external envelope U external-wall = 0.14–0.16 W/(m2·K). In the current study, the potential hygrothermal risks and their effect on highly insulated multi-story apartment building envelope were analyzed. The study contained a set of hygrothermal analyses to ensure the moisture safety of highly insulated facade structures and the selection of materials from the perspective of hygrothermal performance and low risk of degradation. This research found that the risk of mold growth is high if timber elements are installed without protective measures against drying-out built-in moisture, wind-driven rain, and other weather conditions. The initial moisture content of the external concrete slab, to be considered critical, is 90 kg/m3, and the drying out period is longer than the covered with new layers constructions can sustain if a proper vapor control layer is not added between the existing moist wall and installed insulation elements. Furthermore, the wind barrier layer with high thermal resistance and vapor permeability of the installed insulation element helps to minimize the risk of mold growth. A careful analysis and selection of materials allow to design moisture-safe timber frame insulation elements and provide low thermal transmittance of renovated building envelopes. The results showed that before the final design and installation of the insulation elements, a thorough hygrothermal analysis of the original external envelope with actual climatic conditions and moisture loads must be realized.