In September 2021, the La Fossa crater at Vulcano, in Italy, entered a new phase of unrest. We discuss a set of monitoring parameters included in the INGV surveillance network, which closely tracked the sequence of effects related to the crisis. The low-frequency local seismicity sharply increased, while the GPS and tiltmeter networks recorded the inflation of the cone, as an effect of fluid expansion in the hydrothermal system. Gravity variations were probably the effects of fast processes within shallow sources. The anomalies in soil CO₂ flux, fumarole temperature, and in plume SO₂ flux marked the strong increase in the vapor output from crater fumaroles. The signs of the impending crisis had been evident in the chemical and isotopic composition of fumarole gases since July 2021. These geochemical anomalies were clearly indicative of the enhanced input of gases from a magmatic source. In October, the massive degassing also influenced the areas at the base of the cone. In some areas, soil CO₂ degassing and the thermal aquifer recorded strong anomalies. By early November, the crisis reached its acme. Afterward, the monitored parameters started a slow and discontinuous decreasing trend although remaining, some of them, sensibly above the background for several months. The multidisciplinary approach proved decisive for the interpretation of the underlying processes acting in the different phases of the unrest, thus allowing a consistent evaluation of the multiple hazards.