The optimal supply chain configuration for biomass production on a given territory is identified by a two-tier approach, which considers both the environmental and the economic points of view. The first tier performs a quick evaluation of the supply chain, based on simplified assumptions and on average values of the parameters characterizing the geographical territory. The second tier allows for the inclusion of spatially explicit parameters of the territory and realizes a more detailed optimization of the supply chain using a multi-objective Mixed Integer Linear Programming framework. A demonstrative case study is presented for the bio-fuel supply to a centralized electric power plant. The considered supply chain is based on miscanthus, cultivated in marginal terrains and converted to pyro-oil in a number of delocalized plants for long distance shipment. The results obtained from the two tiers of the model provide quantitative information, to support quick and effective decision making on the optimal configuration of the supply chain in terms of plant size, location, transport logistics and cultivation. (C) 2015 Elsevier Ltd. All rights reserved.