This study introduces a novel hydro-pneumatic inerter suspension (HPIS) system for engineering vehicles, aiming at enhancing ride comfort and handling stability. The research focuses on addressing the limitations of conventional suspension systems by incorporating an inerter element into the vehicle suspension. The unique aspects of HPIS, such as nonlinear stiffness and nonlinear damping characteristics of the hydro-pneumatic spring, are explored. Firstly, a half-car dynamic model of the HPIS suspension is established, and an improved simulated annealing algorithm is applied to optimize the suspension parameters. Then, we compare the dynamic performance of different HPIS structures, specifically parallel and series layouts. For practical analysis, a simplified three-element HPIS suspension model is used, and the suspension parameters are optimized by a simulated annealing algorithm at speeds of 10 m/s, 15 m/s, and 20 m/s. Key findings reveal that compared to the traditional suspension system of S0, the front and rear suspension working space of S1 decreased by 40%, 40.1%, 40.2% and 30.7%, 30.8%, 30.9%, while with the body acceleration and pitch acceleration deteriorated by 3.1%, 3.2%, 3.3% and 63.4%, 63.8%, 64.0%. However, the S2 can improve all the dynamic performance and offer better ride comfort and handling stability.