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Waste heat recovery via Organic Rankine Cycle (ORC)-based power units represents one of the most promising solutions to counteract the effects of CO2 emissions on climate change. Nevertheless, several aspects are still limiting its development on the on-the-road transportation sector. Among these aspects, the significant variations of the conditions of the hot source (exhaust gases) are a crucial point. Therefore, the components of the ORC-based unit operate far from the design point if the main operating parameters of the plant are not suitably controlled. The maximum pressure of the cycle is one of the most important variables to be controlled for the importance it has on the effectiveness of the recovery and on safety of operation. In this paper, a wide experimental and theoretical activity was performed in order to define the operating parameters that mostly affect the maximum pressure of the recovery unit. The results showed that the mass flow rate provided by the pump and the expander volumetric efficiency were the main drivers that affect the plant maximum pressure. Subsequently, through a validated model of the expander, a diagnostic map was outlined to evaluate if the expander and, consequently, the whole plant were properly working.