To further improve the ride comfort of commercial vehicles, a seat ISD (Inerter–Spring–Damper) suspension utilizing a mechatronic inerter is proposed in this paper. Firstly, a five-DOF (degree-of-freedom) commercial vehicle seat ISD model was built. Then, the positive real network constraint conditions of a biquadratic impedance transfer function were determined, and the meta-heuristic intelligent optimization algorithm was used to solve the parameters. According to the solution, the impedance transfer function was obtained and the specific network structure was realized by network synthesis. Lastly, this study compares the vibration isolation performance of the mechatronic ISD suspension of the vehicle seat with that of a passive suspension. In comparison to passive seat suspension, the seat mechatronic ISD suspension reduces seat vibration transmissibility by 16.33% and vertical acceleration by 16.78%. Results indicate that the new suspension system can be an effective improvement in ride comfort.