Food waste (FW) can be converted to bioethanol via anaerobic digestion (AD) and catalytic biorefinery processes, and bioethanol can be used as a vehicle fuel. In the present study, a hybrid model framework combining three different models (i.e., process simulation, life cycle assessment (LCA), and supply-chain network (SCN) optimization) is proposed to assess the environmental impacts on FW-based vehicle operation. First, a conceptual design of a large-scale process is simulated for AD and biorefinery processes. The overall energy efficiency of the integrated AD and biorefinery process is estimated to be 16.2%. A "well-to-wheel" LCA of FW-based bioethanol production and vehicle operation in South Korea in 2030, which is a new FW scenario, is performed and compared with the LCA of conventional FW treatment and gasoline-fuel vehicle operation. The LCA results show that the global warming (GW) impacts of the new FW scenario are carbon-negative (−5.58 kg CO 2 equiv. per 1 gal of bioethanol) and 14.1% lower than the GW impacts of the conventional scenario. An integrated SCN optimization model for "well-to-pump" FW-derived bioethanol production and "pump-to-wheel" vehicle operation is then proposed to minimize the total GW impact by simultaneously optimizing both strategic FW management and vehicle operation planning decisions. Three real policy-driven scenario studies (according to the utilization rate of FW valorization to vehicle fuel) were analyzed by the developed hybrid model, and the results show that the GW impacts of each scenario are −0.69, −0.99, and −1.29 kg CO 2 equiv. per 1 gal of bioethanol, leading to carbon-negative impacts by 2030.