This paper describes a comprehensive framework for the development and validation of a model-based robust multivariate controller, which is used to regulate the gas exchange processes of an advanced turbocharged natural gas genset engine. The natural gas genset engine involved in this study features a multi-input and multi-output structure and is highly nonlinear, making it a challenge for which to design a controller. A control design-oriented model describing the dynamics of the studied engine is first developed and validated, using modeling techniques commonly employed for modeling of turbocharged engines. A novel robust model-based multivariate controller is then synthesized to incorporate the significant coupling between the engine actuators (throttle valve, bypass valve, and fuel valve) and the desired control objectives (engine speed, throttle differential pressure, and air-to-fuel ratio). To verify the effectiveness of the synthesized controller, it is compared to a benchmark production controller using an experimentally-validated simulation model. Simulation results indicate the merits of the synthesized robust multivariate controller in terms of better tracking performance (robust multivariate controller reduces steady-state error of engine speed, throttle differential pressure, and AFR at most by 100%, 58.9%, and 100% respectively, compared to benchmark production controller), faster transient response (robust multivariate controller reduces settling time of engine speed, throttle differential pressure, and AFR at most by 74.5%, 47.8%, and 71.2% respectively, compared to the benchmark production controller), and finer coordination among multiple interacted actuators when faced with multifacted control objectives.