While theoretically more efficient than starch-based ethanol production systems, conversion of lignocellulosic biomass to ethanol is not without major challenges. A multi-region, multi-period, mixed integer mathematical programming model encompassing alternative feedstocks, feedstock production, delivery, and processing is developed. The model is used to identify key cost components and potential bottlenecks, and to reveal opportunities for reducing costs and prioritizing research. The research objective was to determine for specific regions in Oklahoma the most economical source of lignocellulosic biomass, timing of harvest and storage, inventory management, biorefinery size, and biorefinery location, as well as the breakeven price of ethanol, for a gasification-fermentation process. Given base assumptions, gasification-fermentation of lignocellulosic biomass to ethanol may be more economical than fermentation of corn grain. However, relative to conventional fermentation processes, gasification-fermentation technology is in its infancy. It remains to be seen if the technology will be technically feasible on a commercial scale.