Carbon dioxide transcritical power cycle (CTPC) systems are considered a new and particularly interesting technology for waste-heat recovery. In heavy-duty truck engine applications, challenges arise from the highly transient nature of the available heat sources. This paper presents an integrated model of CTPC systems recovering heat from a truck diesel engine, developed in GT-SUITE software and calibrated against experimental data, considers the likely fuel consumption improvements and identifies directions for further improvement. The transient performance of four different CTPC systems is predicted over a heavy-heavy duty driving cycle with a control structure comprising a mode switch module and two PID controllers implemented to realize stable, safe and optimal operation. Three operating modes are defined: startup mode, power mode, and stop mode. The results demonstrate that CTPC systems are robust and able to operate safely even when the heat sources are highly transient, indicating a promising potential for the deployment of this technology in such applications. Furthermore, a system layout with both a preheater and a recuperator appears as the most promising, allowing a 2.3% improvement in brake thermal efficiency over the whole driving cycle by utilizing 48.9% of the exhaust and 72.8% of the coolant energy, even when the pump and turbine efficiencies are as low as 50%. Finally, factor analysis suggests that important directions aimed at improving the performance and facilitating CTPC system integration with vehicle engines are: (1) ensuring long-duration operation in power mode, e.g., by employment in long-haul trucks; and (2) enhancing pump and turbine performance.