Identification of challenges for integrated assessment of mitigation measures proposed to improve the ecological and chemical status of water bodies is explored in this paper. These challenges are addressed within a framework proposed for a spatially-distributed cost and effectiveness analysis. Resulting environmental and economic impacts of the implementation of measures are assessed using agro-hydrological and bio-economic modelling with effectiveness and costs calculated at each sub basin level. Cost-effectiveness ratios calculated over a long period of measures implementation depend on the location where measures are applied. Mapping costs and effectiveness at the basin sub-level reveals the locations where implementing a measure (within interval confidence) would be the most cost-effective. To compare measures between themselves, cost-effectiveness ratios can also be calculated for the whole catchment by adding up sub basin total costs, and by assessing effectiveness at the watershed outlet. Advantages and shortcoming of the integrated approach are discussed with challenges to investigate all the uncertainties related to mitigation programmes of agro environmental policies for reducing water pollution.