The Main Building of the School of Engineering at the University of Naples “Federico II” has been for years the core of an experimental program focused on structural and seismic monitoring for risk mitigation and management. The relevance of the case study is dictated by the architectural value of the building and its location in the active volcanic area of Campi Flegrei, which has been recently hit by several earthquakes associated with bradyseism. After some renovation interventions affecting the building in the past years, the old monitoring system installed in 2006 was removed and it has been recently replaced by a new up-to-date vibration based Structural Health Monitoring (SHM) system. This is based on automated Operational Modal Analysis (OMA) and statistical pattern recognition procedures to extract the damage features from ambient vibration measurements, compensate the influence of environmental and operational variables, and perform anomaly detection. The new SHM system has been implemented in the context of a large research project, named RETURN, focused on multi-risk science to create resilient communities under changing climate. In the context of the project, vibration-based SHM plays a pivotal role as a technology to enhance resilience in environments exposed to natural hazards. The present paper describes the implemented SHM system in detail, reporting some preliminary results, remarking the primary role of OMA in the development of effective SHM technologies.