An approach to sustainable intervention on historic buildings is proposed and applied to a case of study, the Church of Santa Maria in Villa in Palestrina. The building presents different forms of degradation including a large amount of moisture in the masonry, widespread salt efflorescence, but above all, floor surface dew. Methodology involves the use of on-site ambient measurements and dynamic simulation to better understand the microclimatic phenomena causing degradation. After a careful historical investigation, an environmental monitoring campaign was carried on, from June 2015 to January 2016 and data analysis was conducted according to European standards for cultural heritage preservation. Dynamic simulation was applied considering heat and moisture transfer through the church envelope. Possible presence of liquid water in the walls did not allow to fully calibrate the simulation model but the investigation was useful to confirm observations. Some interventions have been proposed based on the survey carried on.