With the increasingly strict regulations for energy saving and emission reduction technology of ships, minimizing fuel cost is one of the most critical issues in the design and operation of merchant ships. A method to reduce the fuel cost for merchant ship is to select an economical route based on the real-time meteorological environment and weather forecasting data. So far, numerous ship routing strategies have been proposed with the development of weather routing system. More recently, many wind-assisted devices like rotors, wind sails, etc. have been investigated and designed to utilize the renewable wind energy. With the equipment of wind-assisted rotors, the optimization of ship route becomes more important because the effect of this wind-assisted device highly depends on the local wind field along the ship route. In this paper, an improved optimization strategy with the combination of the A* algorithm and a realtime optimizer has been proposed to determinate the optimal ship route and ship operations including ship heading, propeller’s rpm and rotor’s rpm. The real-time information for the weather conditions, ocean climate and sea states are obtained from European Center for Medium-range Weather Forecasts and the ship performance is evaluated by data-driven models. Finally, the proposed method was applied to test cases of ships operating in Pacific route and Indian Ocean route and the results show that the total fuel consumption could be reduced compared to the minimum distance route.