A simulation analysis model of a 3D-packaging through glass via (TGV) was established. The high-frequency signal characteristics of TGV were analyzed, and the simulation results of the return loss (S11) were obtained. The influences of the signal frequency, type, maximum diameter, height, and minimum diameter of the TGV on the S11 were studied. The maximum diameter, height, and minimum diameter of the TGV were selected as the design parameters, and the S11 at 10 GHz was obtained as the target value. Seventeen groups of experimental simulation calculations were designed using the response surface method, and the relationship between the S11 of the TGV and its key structural parameters was fitted. The fitting model was optimized by combining a genetic algorithm, and the optimal combination parameters of the TGV S11 were obtained as follows:a maximum diameter of 65 μm, height of 360 μm, and minimum diameter of 44 μm. The optimal combination parameters were verified. The simulation results of the optimal combination parameters are 1.593 5 dB less than the S11 of the basic model, and the structure of the TGV is optimized.