Waste heat recovery by means of a CO2 transcritical power cycle (CTPC) is suitable for dealing with high-temperature heat sources and achieving miniaturization. Considering the variable operating conditions of engines, the object of current work is to reveal the influence of design condition selection on CTPC systems. Two different engine operating conditions are chosen for system design. System performance has been predicted by a dynamic model and compared by net power output at off-design conditions. Constraints on temperatures, pressures and pump rotational speed have been taken into account. The results show that system designed under a partial load condition possesses a broad range of operation which will be beneficial to operate continuously when engine condition varies. The operating condition determined by driving cycles is recommended for system design of waste heat recovery for gasoline engines. Optimal performance can be obtained by adopting the mass flow rate guided operation strategy. Moreover, the average fuel consumption reduction during the Highway Fuel Economy Test Cycle over the original is 2.84% if system is designed under a partial condition. These preliminary results give reference to system design and optimization for waste heat recovery of engines based on thermodynamic cycles.