Pompeii Archaeological Park is the best laboratory for the study of the seismic site effects on cultural heritage: the ancient site was destroyed and buried by the 79 AD Vesuvian eruption and, furthermore, it was also affected by the 62-63 AD strong earthquake. Large sectors of the city were reconstructed after this earthquake while other parts were still under reconstruction when the fallout and pyroclastic density currents of the eruption buried the Roman city. In order to evaluate the distribution of the damage and reconstructions due to the earthquake, detailed mappings of the structures were carried out using multidisciplinary approaches. In addition, analyses of the topographical features, subsoil stratigraphies, and geophysical surveys, responsible for local seismic amplification (site effects), allow us to define the sectors of the ancient city where the Amplification Factors (AFs) were the main ones responsible for damage. Selected areas and examples of compromised and reconstructed buildings show that the ancient topography and subsoil features (both lithological and seismic) are the main AFs. In particular, the damages caused by the 62-63 AD earthquakes seem to be mainly due to topographical factors such as steep scarps and slopes, ridges, peaks, and terraces, as well as to the major thickness of the soft sediments (loose volcanoclastic layers, paleosols, weathered lavas, and anthropogenic infillings) located over the well-lithified lavas. It is not uncommon to also have the combination of these two factors. For the first time, this multidisciplinary approach allows us to draw a seismic microzonation map for one of the most important archaeological sites of the world.