In this paper, a combined organic Rankine cycle (ORC) system that can effectively utilize the cold energy of Liquefied Nature Gas (LNG) and the waste heat of dual fuel (DF) marine engine was proposed. Particularly, the engine exhaust gas and the jacket cooling water of the DF marine engine were used as heat sources. Firstly, a thorough assessment of thermo-economic performance was conducted for the combined ORC system using 11 environmentally friendly working fluids (WFs). Afterwards, the effects of evaporation and condensation pressures on the net output work, energy efficiency, exergy efficiency, total investment cost and payback period were examined. Furthermore, the thermo-economic performances of the ORC system were optimized via multi-objective optimization with a genetic algorithm. Finally, exergy destructions and investment costs of each component under the optimal operating conditions were analyzed to make suggestions for further improvement. The results show that R1150-R1234yf-R600a and R170-R1270-R152a are the two most promising WF combinations. The exergy destruction of the combined ORC system mainly exists in heat exchangers. Through WF optimization, the exergy destruction in the intermediate heat exchanger was reduced by 18.99%. The proportion of expanders investment cost could be greater than 50% and the payback period of the combined ORC system varies in the range of 7.68–9.43 years. This study demonstrated that the selection of WF and the optimization of operating conditions had important potential to improve thermo-economic performances of ORC systems.