Several of the world’s active volcanoes are located near densely populated areas, and therefore the seismic hazard associated with preeruptive earthquake activity and its relation to the potential damage of engineering structures should be considered as a part of risk evaluation and management. This is true for Mt. Vesuvius volcano (southern Italy), where several hundred thousand people are exposed to volcanic and related seismic risks. This study investigates the effect of preeruptive seismic activity through the massive simulation of earthquake waveforms in the magnitude, location, and focal-mechanism ranges expected for Mt. Vesuvius seismicity. Synthetics are processed to evaluate the characteristic strong-motion parameters, which are useful for estimating the seismic damage to a built-up environment that would arise from both the maximum expected single event and the cumulative effect of a large number of small events. Synthetic and observed strong-motion parameters for a selected set of recorded earthquakes are compared to validate the modeling approach. The scaling of the simulated peak ground acceleration (pga) with distance appears to be influenced by earthquake depth, owing to the presence of a sharp velocity discontinuity at shallow depths underneath the Vesuvius area. On the other hand, the hysteretic energy spectrum, related to the plastic behavior of the structures, depends strongly on the b-parameter of the Gutenberg–Richter law (G–R). By varying the G–R law parameters across a reasonable expected range, we observe that the cumulative hysteretic energy is comparable to the values observed at near-source distances during the 1997 Umbria-Marche, Italy, event (M 5.8), which produced serious damage to buildings and infrastructure, although a significant pga value was not recorded.