Abstract Enhancing durability and service life of buildings and components is pivotal for sustainable development. It constitutes an opportunity to reduce energy consumption, carbon emissions and life cycle impact of buildings in a climate neutral perspective. Issues strongly introduced and set as priorities by EU policies that highlight the urgent need to tackle them also through deeply heritage renovation and digital transformation in the building sector. Digitalization is a cornerstone of this transformation, instrumental in facilitating and enabling it sustainably. The Key Enabling Technologies (KETs) are directly associated with new technological potential and emerging technologies. Digital Twin (DT) approach appears alongside these. Its experimentation and widespread application are gaining prominence in innovating Life Cycle Management (LCM) and sustainability practices of buildings. In this scenario the paper explores the role and potentialities of DT approach presenting the experimental application of the DT4SEM. A digital infrastructure that, by integrating Internet of Things (IoT), synchronizes a physical building with its virtual counterpart. The two realities (physical and virtual) remain interconnected through the mutual exchange of data, both in real-time and asynchronously enabling proactive monitoring and analysis of seismic behaviour. The experimental setup involves simultaneously Big Data analytics, simulation tools and deploying sensors within the sample building. Data is then fed into the virtual DT model, allowing for continuous comparison and analysis to detect anomalies and predict potential risks. This approach facilitates enhanced decision-making, performance optimization and sustainability improvements across the building’s lifecycle: a new vision for built environment management that evolves from a process resulting in a sequence of operative phases into a complex digital infrastructure. The design of the DT4SEM and the current application for seismic monitoring in buildings, results from a collaborative effort involving the academic spinoff BIG srl, the startup Sysdev, the company Berna Engineering srl, and ACCA Software spa.