This project aims at finding cost-efficient sets of measures to meet the Water Framework Directive (WFD) derived goals for the Dommel River (The Netherlands). Within the project, both acute and long-term impacts of the urban wastewater system on the chemical and ecological quality of the river are studied with a monitoring campaign in the urban wastewater system (wastewater treatment plant and sewers) and in the receiving surface water system. An integrated model, which proved to be a powerful tool to analyse the interactions within the integrated urban wastewater system, was first used to evaluate measures in the urban wastewater system using the existing infrastructure and new real-time control strategies. As the latter resulted to be beneficial but not sufficient, this paper investigated the use of additional infrastructural measures to improve the system cost-effectively and have it meet the Directive's goals. Finally, an uncertainty analysis was conducted to investigate the impact of uncertainty in the main model assumptions and model parameters on the performance robustness of the selected set of measures. Apart from some extreme worst-case scenarios, the proposed set of measures turned out to be sufficiently robust. Due to the substantial savings obtained with the results of this project, the pay-back time of the whole monitoring and modelling work proved to be less than 5 months. This illustrates the power of mathematical modelling for decision support in the context of complex urban water systems.