This study focuses on the application of a hygro-thermo-mechanical (HTM) model to evaluate the structural behaviour of full-scale buildings, using a historical masonry structure as case study. In particular, the former Civic Tower of Pavia (Italy) was selected due to its simple morphology, unique historical significance, loading conditions, and the comprehensive set of structural information and material data available from previous studies. First, the proposed HTM model is introduced, including its components, namely the moisture transport model, heat transfer model, and mechanical model. Within this framework, the heat and moisture fields are fully coupled, whereas one-way coupling is employed between the hygrothermal and mechanical fields. Subsequently, the HTM model is applied to the Civic Tower of Pavia, with focus on the effects of moisture and temperature on the structural response. The results of the analysis are presented and dis-cussed in terms of developed stresses at the base of the building. Special attention is given to how moisture and temperature affect the mechanical behaviour of masonry, including potential for damage and failure under severe scenarios. This study offers a comprehensive overview of the HTM model and its practical application in a full-scale case study. The results highlight the critical importance of considering moisture and temperature effects in the design and maintenance of masonry structures, particularly in historical buildings. The paper concludes with recommendations for future research in this area, including the development of more advanced modelling techniques and the acquisition of additional data concerning the behaviour of masonry structures under varying environmental conditions.