Abstract The fruit and vegetable sector generates large amounts of waste, which poses both environmental and economic issues. Different strategies can be applied to valorise fruit and vegetable waste (FVW) by turning it into value-added products. However, the economic and environmental impact of such strategies is largely unknown. In this paper, the environmental and economic impact of FVW valorisation on an industrial scale was evaluated by developing a Decision Support System (DSS). To this aim, the lettuce waste study-case was considered, since different innovative laboratory-scale strategies have been recently proposed for its valorisation. Investment and running costs, energetic demand and yields of lettuce waste valorisation processes were collected based on laboratory tests and industrial surveys. The application of the DSS estimated that if 30% of lettuce waste annually produced by a large company was valorised by using a system configuration that involves not only anaerobic digestion and composting, but also high pressure homogenisation to produce fresh juices, and ultrasound-assisted extraction to produce antioxidant extracts, this configuration would lead to an investment lower than 10 million €, a 1 year-pay-back time and a 72 tons-reduction of carbon dioxide emissions, thus representing a rational compromise between economic returns and environmental advantage. The developed multi-objective DSS is a valuable tool to identify the most sustainable and investment-worthy processes for the valorisation of FVW.