SummaryConnectivity is a key element enabling intelligent vehicles to communicate with each other and the Smart Road. In general, the connectivity is allowed by an On‐Board Unit enabling the Vehicle to Everything communication. This paper proposes an innovative unit acting not only as a device allowing connectivity but also as an intelligent electronic control unit to perform advanced and adaptive control strategies able to give reference trajectories and actuator set‐points to the low‐level control systems of power‐train and vehicle dynamics. In particular, based on a cascade model predictive control, an adaptive control strategy is proposed, considering time‐varying parameters and information related to vehicle kinematics and dynamics. Such a strategy allows the vehicle to follow a certain origin‐destination path in the inertial frame, based on an upper controller that considers a vehicle kinematic model so as to give speed references and target values for the steering angle at the wheels to the inner predictive control loop acting on both longitudinal and lateral vehicle dynamics. To check the effectiveness of the proposed approach, a comparison is made with existing cascade control strategies. The results show better safety and lane‐keeping performance. Then, using Hardware‐In‐the‐Loop testing for the proposed Intelligent On‐Board Unit, the considered approach demonstrates robustness against parametric variations, signal delay and noise both in the Global Positioning System and in the yaw rate sensor. The achieved results show good robustness properties, safety performances and confirm the real‐time execution of the cascade control strategy, paving the way to future developments necessary before tests in a real road scenario.