The organic Rankine cycle (ORC) system is an important technology for recovering energy from the waste heat of internal combustion engines, which is of significant importance for the improvement of fuel utilization. This study analyses the performance of vehicle ORC systems and proposes a rapid optimization method for enhancing vehicle ORC performance. This study constructed a numerical simulation model of an internal combustion engine-ORC waste heat recovery system based on GT-Suite software v2016. The impact of key operating parameters on the performance of two organic Rankine cycles: the simple organic Rankine cycle (SORC) and the recuperative organic Rankine cycle (RORC) was investigated. In order to facilitate real-time prediction and optimization of system performance, a data-driven rapid prediction model of the performance of the waste heat recovery system was constructed based on an artificial neural network. Meanwhile, the NSGA-II multi-objective algorithm was used to investigate the competitive relationship between different performance objective functions. Furthermore, the optimal operating parameters of the system were determined by utilizing the TOPSIS method. The results demonstrate that the highest thermal efficiencies of the SORC and RORC are 6.21% and 8.61%, respectively, the highest power outputs per unit heat transfer area (POPAs) are 6.98 kW/m2 and 8.99 kW/m2, respectively, the lowest unit electricity production costs (EPC) are 7.22 × 10−2 USD/kWh and 3.15 × 10−2 USD/kWh, respectively, and the lowest CO2 emissions are 2.85 ton CO2,eq and 3.11 ton CO2,eq, respectively. The optimization results show that the RORC exhibits superior thermodynamic and economic performance in comparison to the SORC, yet inferior environmental performance.