The island of Ischia, an active volcanic field emerging in the western sector of the Gulf of Naples (Southern Italy), represents an archetypal case of caldera that underwent a very large resurgence related to the intrusion of a shallow magma body. The resurgence culminated with the formation of a structural high in the central sector of the island, i.e., the Mt. Epomeo block. This is bordered by a system of faults along which volcanic activity occurred up to 1302 A.D., and damaging earthquakes were generated in historical and recent time. The seismicity is located prevalently in the northern sector of the island and appears to be correlated with the most recent phase (<5 ka) of ground movement (subsidence), although the mechanism of earthquakes’ generation is still debated. By jointly analyzing offshore and onshore data (seismic profile and stratigraphy wells, respectively) and new petrological and geochemical data related to the most recent phase of volcano-tectonic activity, we develop a geological and structural layout of the northern sector of the island. In particular, we identify the seismogenic fault associated with the historical and recent destructive earthquakes of Ischia. This fault formed in the northern sector of the island during the final stage of the resurgence. We also propose a conceptual volcano-tectonic model of the northern sector of the Ischia Island, depicting the displacement of the fault zones in the off-shore area and the possible mechanism of stress loading and release in the on-shore zone, which is mainly driven by the subsidence of the Mt. Epomeo block. Our results are crucial for evaluating the dynamics of the seismogenic structures in the framework of the general subsidence of the island, as well as the related seismic hazard.