The medieval walls, preserved in various urban centers, tell the story of the formation of the cities they surround. These structures, built at different times and with different materials, are subject to deterioration and collapse over time. Monitoring their structural integrity is crucial for preservation, but also for the safety of the inhabitants. In areas with significant seismic activity, exacerbated by climate change, these structures face demands for which they were not designed. This study presents the initial development of a Digital Twin (DT) for Gubbio’s medieval wall, integrating multiple data sources and advanced simulation techniques to enhance heritage conservation. The DT framework combines a high-fidelity Building Information Model (BIM) derived from UAV-based photogrammetry and point cloud data, and continuous Structural Health Monitoring (SHM) measurements (temperature, humidity, and tilt) collected from 2018 to 2024. A detailed time series analysis of the sensor data revealed distinct seasonal and daily patterns, while a Solar Radiation Analysis (SRA) provided the necessary thermal load information. These insights informed a fully coupled thermal-mechanical analysis through a Finite Element Model (FEM) developed in Abaqus, which accurately replicated short-term rotational variations—captured over 15-day windows—induced by environmental loads. The results underscore the importance of a multi-physics approach in understanding the complex interactions affecting heritage structures. Moreover, this work lays the foundation for future advancements in real-time sensor-to-model integration, uncertainty quantification, and AI-driven predictive maintenance, thereby supporting proactive preservation strategies under changing environmental conditions.