The continuous rise of oil price signifies the increasing necessity to move towards renewable resources of energy. One much promising energy resource is the conversion of biomass to ethanol, and therefore the Department of Energy is working to develop cost effective, environmentally friendly biomass conversion technologies. There are various pathways to conversion of biomass to ethanol. These technologies, however, are new and there are uncertainties associated with the performance as well as costs of these technologies. This research paper proposes different design process options for the structure of a bio-refinery plant, as well as estimation of individual equipment parameters in order to optimize critical objectives such as cost, plant efficiency and gas emissions. The design of bio-refineries could engage several process option alternatives. In order to find the optimal pathways as well as optimal design, researcher will use the optimization approach to process synthesis and design. The methods need to handle both discrete decisions like crop selection, energy option selection and process synthesis options, and continuous decisions such as the process parameters. Uncertainties are inherent in models, objectives and data. Therefore, the proposed study also focuses on the development of an integrated framework based on efficient multi-objective optimization under uncertainty algorithms. To be economically viable, ethanol production cost must be under the market value of ethanol. The Department of Energy has set a goal selling price of $1.07 per gallon for 2010. The process design and economic model will give insights for further reduce of cost and set priorities for future research.