The Italian Institute for Environmental Protection and Research (ISPRA) manages the national sea state real time monitoring system for Italy, which consists of the National Sea Level Network (RMN), the North Adriatic and Venice Lagoon Sea Level Network (RMLV), the National Wave Networks (RON), and a marine weather forecasting system. These systems are particularly deployed to monitor and predict storm surges that affect the northern part of the Adriatic Sea and the Venice Lagoon, usually causing damages and morphological impacts over the highly anthropized coastal areas. On 22 November 2022, an extreme storm surge event occurred in the northern Adriatic Sea, producing severe damages on its coastline. Venice and the surrounding urban settlements have been protected from flooding thanks to the operation of the Mo.S.E. (Modulo Sperimentale Elettromeccanico) system, a set of artificial barriers built to isolate the lagoon from the sea in case of extreme high tides. Coastal flooding prevention measures, such as storm-surge barriers, are indeed being widely adopted globally because of the accelerating rise in sea levels. An analysis of this extreme event is presented here to highlight the functionality and the usefulness of the ISPRA sea state monitoring system. In particular, the analysis of the as-if scenario reproducing the natural tide propagation within the lagoon, neglecting the operation of the Mo.S.E. system, can only be pursued by using hydrodynamic models forced using extensive observed data. Results highlight that the “not-regulated” sea level would have exceeded 200 cm above the reference datum at Chioggia, a threshold never recorded in the Venice Lagoon since sea level monitoring systems have been operational.