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This work explores the possibilities of improving the eco-efficiency of Wastewater Treatment Plants (WWTPs) introducing a plant-wide perspective in the formulation of the control strategy. Eco-efficiency goals are contemplated in the analysis of the appropriateness of control actions, considering the seasonal effects of temperature into the decision-making process. Plant-wide control strategy handles are the operation variables of the activated sludge process, the volume of the primary clarifier, and the temperature of the anaerobic digester. Performance is evaluated in terms of energy use, biogas production, effluent quality, emissions to air and soil, considering annual and bimestrial average values of indicators to capture seasonal effect of temperature. The result is a set of possible solutions, obtained from a multi-objective decision-making procedure, consisting on a sequence of control actions applied at different temporal windows that improve the eco-efficiency indicators of the plant. The results obtained when applying the different solutions make evident how the application of plant-wide control strategies is useful to improve performance indicators that represent individual goals, leading to trade-off solutions that describe WWTPs’ eco-efficiency.