The Jiangsu-South Yellow Sea area is located on the East Asian Continental Margin and at the junction of South and North China. It is one of the high seismicity areas in eastern China. To enhance our understanding of the relationship between disastrous earthquakes and the geophysical properties of Earth materials, P- and S-wave travel-time data over the past 20 years are inverted to image the 3D distributions of seismic velocity (VP and Vs) and Poisson’s ratio (σ). The results show that the velocity and Poisson’s ratio demonstrate congruence with the prominent geological formations present within the study area. Specifically, the velocity models for the upper crust at depths of 5, 10, and 15 km. We found that within the total study area, 70% ± 7.2% of M5+ earthquakes that occurred during the past decades initiated in the VP tomographic edge zones (TEZ). Moreover, the distribution patterns of M5+ earthquakes in the offshore sea region exhibit significant differences when compared to those in the Jiangnan Orogenic Belt. In the offshore sea region, about 66.7% ± 8% of M5+ earthquakes initiated in the velocity and Poisson’s ratio TEZ. The presence of comparatively low Vs and high Poisson’s ratio anomalies in the Wunansha Uplift suggest the potential existence of fluids. The triggering mechanism for these earthquakes can likely be ascribed to the presence of hydrothermal fluids and the reactivation of preexisting strike-slip faults, influenced by the subduction of the Pacific and Philippine Sea Plates, as well as the collision between the India and Eurasia Plates. In contrast, within the Jiangnan Orogenic Belt, M5+ earthquakes predominantly initiated in the high-velocity and low Poisson’s ratio perturbation zones. The primary factor contributing to seismotectonic features disparities are likely the variation in fluid content. We infer the rock matrix in the vicinity of the source region of the Jiangnan Orogenic Belt is presumed to be drier, more brittle, and possess greater mechanical strength.