This study investigates the economic and environmental benefits of integrating hydroprocessing, fermentation, and anaerobic digestion into a pyrolysis refinery. Two scenarios were developed for upgrading and/or utilizing the primary products of pyrolysis (bio-oil, gas, and char). The first (hydroprocessing) scenario hydroprocesses whole bio-oil into gasoline and diesel. The second (fractionation) scenario fractionates bio-oil into sugars for fermentation to cellulosic ethanol and residual phenolic oil as the primary product. Both scenarios use the gaseous product of pyrolysis for process heat in the plant and employ biochar to enhance anaerobic digestion of manure for power generation. The fast pyrolysis plant processes 2000 ton/day of corn stover while the anaerobic digester employs 430 ton/day of manure to generate power. The hydroprocessing scenario produces gasoline at a minimum fuel-selling price (MFSP) of $2.77 per gallons of gasoline while the fractionation scenario produces ethanol and phenolic oils (diesel) as a transportation fuel for $1.2 per gallon ($1.41 per GGE). Sensitivity analysis indicates that the MFSP for both scenarios is highly sensitive to the fixed capital cost. Fixed capital costs for the hydroprocessing and fractionation scenarios were estimated to be $643 and $288 million, respectively. Fuel production rates for the hydroprocessing and fractionation scenarios are 60.5 and 16 million GGE per year, respectively. Life cycle greenhouse gas emissions were calculated as −9.6 and −16.6 g CO2,eq per MJ for the hydroprocessing and fractionation scenarios, respectively. LCA emissions are sensitive to byproduct credits derived from biochar sequestration and power generation. This study shows that both systems produce transportation fuels at competitive market prices with an additional reduction in atmospheric CO2 levels compared to fossil fuel sources.