Steep slopes mantled by pyroclastic deposits are favorable areas prone to generate hazardous volcaniclastic flows. In Italy, such a setting is well represented in the Campania Region, where pyroclastic deposits from the explosive activity of the Neapolitan volcanoes (Ischia, Campi Flegrei, and Somma-Vesuvius) cover the Apennine range bordering the Campanian Plain. In order to provide a useful contribution to the mitigation and prevention of these calamitous natural events, this work presents a multidisciplinary approach to improve the understanding of the volcaniclastic flow hazard zonation in an Apennine area of 340 km2 surrounding the Somma-Vesuvius volcano. The disruption proneness index (DPI) was calculated in order to identify the drainage basins potentially prone to generate volcaniclastic flows. This index is obtained by combining satellite and morphometric data in a geographic information system (GIS) environment. It is calculated for 1100 drainage basins, considering the main parameters influencing the slope stability (slope angle, basin shape factor, curvature, relative relief, aspect, and land cover). The land cover mapping is obtained from Landsat data and airborne high-resolution images, while the morphometric parameters are derived from a digital elevation model (DEM) with a cell size of 10 m. The result is a zonation map that classifies the drainage basins according to different degrees of proneness to generate volcaniclastic flows (low, moderate, high, and very high). The drainage basins falling within high and very high classes are 66%, while 28% fall in the moderate class, and the remaining 6% fall in the low proneness class.