In the context of environmental sustainability there has been an increasing interest in bioenergy production from renewable resources, and is expected that European biofuel production from energy crops will increase as a consequence of the achievement of policy targets. The aim of this paper is to assess the agronomic feasibility of biomass crop cultivation to provide profitable renewable feedstocks in a marginal and heavy-metal polluted area located in the Sulcis district, Sardinia (Italy). Results from literature review and unpublished data from field trials carried out in Sardinia were analysed to establish the main agronomic traits of crops (e.g., yield potential and input requirements). A Geographical Information System (GIS)-based procedure with remotely sensed data is also used to evaluate the land suitability and the actual land use/cover, considering a future scenario of expansion of energy crops on these marginal areas avoiding potential conflicts with food production. The results of the review suggests that giant reed, native perennial grasses and milk thistle are the most suitable energy crops for this area. The land suitability analysis shows that about 5700 ha and 1000 ha could be available for feedstock cultivation in the study area and in the most polluted area, respectively. The results obtained from land suitability process and agronomic evaluation will serve as a base to support technical and economical feasibility studies, as well as for the evaluation of environmental sustainability of the cultivation in the study area.