The transition to a sustainable building industry requires higher insulation levels to reduce operational energy consumption. However, this can lead to higher embodied energy. Hence, bio-based materials like lime hemp are gaining interest, both in new projects and in renovation strategies, e.g. as interior retrofit for existing masonry. This study investigates hybrid façade systems comprising an outer masonry leaf and interior timber frame with bio-based insulation. The aim is to gain insight on the thermal inertia and hygrothermal performance of lime hemp. Both on-site measurements and 1D Heat, Air and Moisture (HAM) simulations in Delphin 6 are used to evaluate performance under varying conditions of orientation, moisture content and solar radiation. The thermal inertia of bio-based materials is often considered a benefit but can be affected by the wall’s moisture behaviour. The watertightness of the wall system relies on the outer masonry leaf. When infiltrations occur, the moisture-buffering capacity of the bio-based insulation is activated. This becomes a challenge due to the hygroscopic nature of bio-based materials, as excessive moisture accumulation can lead to degradation or performance losses of the hybrid wall system. Therefore, this study emphasizes the importance of moisture buffering, rainwater management, and drying potential. The monitoring campaign on a recently built case study reveals that the east orientation demonstrates higher thermal inertia than the southwest, with time lags up to 14 h for 26 cm of lime hemp. While simulations confirmed the latter, the relative humidity was underestimated and thermal inertia was overestimated compared to the measurements.