Abstract The growing global demand for fresh water coupled to the increasing interest in renewable energies and waste heat recovery has resulted in flourishing attention to the multi-effect distillation process for seawater desalination. The low operating temperature makes this technology attractive in the case of low temperature heat sources such as geothermal, solar or waste heat recovery. The low energy density of these heat sources requires small-scale desalination systems whose layout and operation may differ from large-scale plant. In this work, new plant configurations for a small-scale multi-effect distillation system are proposed and analyzed from a thermodynamic and economic point of view. Each configuration tends to better exploit the energy content of the various streams by improving heat recovery, according to an increasing layout complexity. These configurations were studied in two layouts, differing in the way seawater and brine fed the various effect. The feed mass flow in each effect was varied to maximize the recovery ratio by imposing the maximum salt concentration in the brine related to calcium sulphate precipitation. Numerical simulations were conducted in Aspen Plus environment by varying the top brine temperature with a fixed bottom brine temperature of 40 °C. The electrolyte non-random two liquid equation of state was adopted to evaluate saltwater properties and an inter-model comparison with a validated algebraic model was carried out. The configurations implementing seawater preheating increased the performance ratio up to 10% due to the better exploitation of the energy content of distillate streams. The proposed solutions with the maximization of the recovery ratio demonstrated to be cost-effective with respect to the base multi-effect distillation configuration when thermal energy cost became relevant. In the case of negligible thermal energy cost (waste heat recovery) the base configuration was the preferable solution in terms of water cost, despite the lower performance ratio.