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Renewable liquid biofuels for transportation have recently attracted enormous global attention due to their potential to provide a sustainable alternative to fossil fuels. In recent years, the attention has shifted from first-generation bioethanol to the production of higher molecular weight alcohols, such as biobutanol, from cellulosic feedstocks. The economic feasibility of such processes depends on several parameters such as the cost of raw materials, the fermentation performance and the energy demand for the pretreatment of biomass and downstream processing. In this work, two conceptual process scenarios for isobutanol production, one with and one without integrated product removal from the fermentor by vacuum stripping, were developed and evaluated using SuperPro Designer®. In agreement with previous publications, it was concluded that the fermentation titer is a crucial parameter for the economic competitiveness of the process as it is closely related to the energy requirements for product purification. In the first scenario where the product titer was 22 g/L, the energy demand for downstream processing was 15.8 MJ/L isobutanol and the unit production cost of isobutanol was $2.24/L. The integrated product removal by vacuum stripping implemented in the second scenario was assumed to improve the isobutanol titer to 50 g/L. In this case, the energy demand for the product removal (electricity) and downstream processing were 1.8 MJ/L isobutanol and 10 MJ/L isobutanol, respectively, and the unit production cost was reduced to $1.42/L. The uncertainty associated with the choice of modeling and economic parameters was investigated by Monte Carlo simulation sensitivity analysis.