This paper studied the inhomogeneity of crustal medium in Jiangsu-Shandong segment of the Tanlu fault zone from large- and small-scale aspects. Using seismic data, the inhomogeneity of velocity structure, unit virtual wave, and Poisson ratio of crustal media were studied. The length of seismic source of the Tancheng M8.5 earthquake that occurred in 1668 was calculated, and the source region boundary along the Tanlu fault zone was determined. The locking section, accumulation unit, and adjustment unit of seismic stress were determined according to seismogenic tectonics and seismicity. Through analysis of the crustal media of the Tancheng M8.5 earthquake and various inhomogeneity parameters, we inferred that the possible region of future large earthquake is the NNE direction region with the range of 33°-34.5°N, 118°-118.8°E, and the highest magnitude can reach M8.