Waste heat recovery (WHR) for internal combustion engines in vehicles using organic Rankine cycle (ORC) has been a promising technology recently. The operation of the ORC WHR system in supercritical conditions has a potential to generate more power output and thermal efficiency compared with the conventional subcritical conditions. However, in supercritical conditions, the heat transfer process in the evaporator, the key component of the ORC WHR system, becomes unpredictable as the thermo-physical properties of the working fluid changes with the temperature. Furthermore, the transient heat source from the vehicle’s exhaust makes the operation of the WHR system difficult. This paper investigates the performance of the ORC WHR system at supercritical conditions with engine’s exhaust data from real city and highway drive cycles. The effects of operating variables, such as refrigerant flow rates, evaporator and condenser pressure, and evaporator outlet temperature, on the performance indicators of the WHR system in supercritical conditions are examined. Simulation of operating parameters and the boundary of the WHR system are also included in this paper.