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This paper presents the mathematical basis and some illustrative examples of a model-based decision-making method for the automatic calculation of optimum design parameters in modern Wastewater Treatment Plants (WWTP). The starting point of the proposed methodology is the mathematical modelling of the main processes inside a plant's units. The procedure for the automatic calculation of the design parameters is then based on expressing the optimum WWTP design problem as a Mathematical Programming (Optimisation) Problem that can be solved using a non-linear optimisation algorithm (GRG2). The paper shows how the proposed methodology is able to achieve optimum WWTP design using either a steady-state or dynamic mathematical model of the plant and a set of constraints associated with the permitted operational ranges and the required water quality in the effluent. As an illustrative example to show the usefulness of the proposed methodology, the optimum design of the Step-Feed process for nitrogen removal (Alpha) has been analysed by considering two different problems: the optimum plant dimensions, estimated at critical temperature for effluent requirements (Problem 1), and the optimum selection of facultative volumes, fractions of the influent flow-rate and the values of oxygen set-points for long-term plant operation (Problem 2). The proposed decision-making method is intended to facilitate the task of the engineers involved in the design of new WWTP, especially when the complexity of the plant requires a systematic procedure for the selection of the main design parameters.