Climate change mitigation has become a binding driver in biofuels production. First generation bioethanol, initially indicated as the most competitive option, is now incurring in ever increasing discredits forcing the transition towards more sustainable productions (i.e. second and third generation technologies). This paper addresses the strategic design and planning of corn grain- and stover-based bioethanol supply chains through first and second generation technologies. A Mixed Integer Linear Programming framework is proposed to optimise the environmental and financial performances simultaneously. Multi-period, multi-echelon and spatially explicit features are embodied within the formulation to steer decisions and investments through a global approach. A demonstrative case study is proposed involving the future Italian biomass-based ethanol production. Results show the effectiveness of the optimisation tool at providing decision makers with a quantitative analysis assessing the economic and environmental performance of different design configuration and their effect in terms of technologies, plant sizes and location, and raw materials. (C) 2011 Elsevier Ltd. All rights reserved.