Brownfields redevelopment is an issue of increasing concern for urban planners and decision-makers, especially in highly industrialized countries. As the multidisciplinary scientific literature on brownfields redevelopment continues to grow - usually targeted at the scale of a single site - the challenge becomes more and more important when it comes to managing the redevelopment at the level of a portfolio of sites. This article presents a novel approach aiming the systematization of an ex-ante economic analysis of brownfield redevelopment at the scale of a large industrial area. We have developed a decision support tool based on constrained optimisation and cost-benefit analysis to identify the economically optimal combination of redevelopment choices for a given portfolio of sites and future use alternatives. This approach incorporates: (1) the costs and benefits of brownfields redevelopment; (2) sites characteristics and compatibility with future-use alternatives; (3) regulatory requirements and regional policy orientations; and (4) synergies or interactions between sites and future-use alternatives. The implementation of the modelling exercise is illustrated with the case study of the Vallée de la Chimie, for which the model enabled to find an economically optimal solution and then to explore different scenarios. Results demonstrate that portfolio scale analysis offers relevant economic information for decision-making. Urban-planning experts from Lyon metropolis who are in charge of the case study signalled that the tool offers relevant support for exploratory studies, especially by using it to compare different scenarios based on different prospective evaluations. Therefore, we argue that there is scope for further development of portfolio-scale decision support tools as a complementary approach for the well-known single-site scale best practices.