The catalytic hydrogenation of lignocellulosic derived bio-oil was assessed from the thermodynamic simulation perspective, in order to evaluate its economic potential for the production of added-value chemicals and drop-in fuels. A preliminary economic evaluation was first run to identify the conditions where the process is profitable, while a full economic analysis evaluated how the operating conditions affected the reaction in terms of yield. The results indicate that the bio-oil should be separated into water-soluble and insoluble fractions previous hydrogenation, since very different process conditions are required for the two portions. The maximum economic potential resulted in 38,234 MM$/y for a capacity of bio-oil processed of 10 Mt/y. In the simulated biorefinery, the insoluble bio-oil fraction (IBO) was processed to produce biofuels with a cost of 22.22 and 18.87 $/GJ for light gasoline and diesel, respectively. The water-soluble bio-oil fraction (WBO) was instead processed to produce 51.43 ton/day of chemicals, such as sorbitol, propanediol, butanediol, etc., for a value equal to the market price. The economic feasibility of the biorefinery resulted in a return of investment (ROI) of 69.18%, a pay-out time of 2.48 years and a discounted cash flow rate of return (DCFROR) of 19.11%, considering a plant cycle life of 30 years.