Severe weather conditions and urban intensification are key factors affecting the response of combined sewer systems, especially during storm events. In this regard, the capacity assessment of combined sewer networks under the impact of rainfall storm events of different return periods was the focus of this work. The selected case study area was a mixed-use catchment in the city centre of Thessaloniki, Greece. The hydraulic performance of the examined sewer network was assessed using an InfoWorks ICM model. The results indicated that mitigation strategies, such as the application of nature-based solutions (NBSs) or low-impact developments (LIDs) are considered essential for controlling combined sewer overflows. A multicriteria analysis was conducted to select the most appropriate NBSs/LIDs to be located in the study area to enhance the system’s capacity. The results of this multicriteria analysis were used to propose a combined sewer overflow mitigation scenario, based on the installation of green roofs, as the most highly ranked solution in the analysis performed. Incorporating the proposed NBS/LID in the hydrologic-hydraulic model significantly increased the performance of the studied combined sewer network.