The projected increase in ‘water scarcity – water reuse’ situations, the associated risks and sustainability challenges, and trends towards holistic approaches motivate the development of integrated assessment for decision-making. The integrated Risk and Sustainability Assessment (RSA) Framework combines the analysis and evaluation of both risk and sustainability of ‘water scarcity – water reuse’ situations. This work aims to test the RSA Framework in a case study in Chile. The analysis uses a multi-layer approach and lane-based approach to translate the real-world system into an information system and to determine interlinkages between indicators. The evaluation involves thresholds and weights to calculate risk and sustainability sub-indices and an RSA index applying TOPSIS. The results indicate low interlinkage between risk and sustainability indicators, visibilising the importance of which and how indicators are considered and what they measure. They show a higher than tolerable degree of risk but an acceptable degree of sustainability. The relevance of spatial and temporal scales for the assessment becomes evident. Spatial aspects are key in determining the degree of water scarcity and how the impact of water reuse can be included in its calculation. Temporal aspects complicate the integration of risk (scenario-based) and sustainability (snapshot mode) assessments. The TOPSIS method appears to be suitable for the aggregation of risk and sustainability performance indicators. Altogether, the results show the potential of the RSA Framework for organising and processing information required to support decision-makers addressing ‘water scarcity – water reuse’ situations from the perspectives of risk and sustainability.