The prices of the bio-diesel and bio-gasoline are normally significantly high when compared to the petroleum-derived fuels. The co-processing of bio-oil and vacuum gas oil in a fluid catalytic cracker (FCC) has been proposed to utilize existing refinery infrastructures while lowering bio-fuel prices. Nonetheless, the integration of the bio-oil production and the existing refinery remains unknown. In this work, a superstructure model is proposed to design and optimize the co-processing process by selecting the optimal biomass feedstock and the bio-oil production process (fast pyrolysis or catalytic pyrolysis). Furthermore, the impacts of the FCC processing capability and bio-oil co-processing ratio on the economics as well as the selection of bio-oil production process are also investigated. As revealed by the results of two scenarios, pulpwood is the optimal biomass feedstock and the fast pyrolysis ought to be selected for producing bio-oil when its co-processing ratio and the FCC processing capability are both relatively high.