Most sewage collection systems designed between 19th and early to mid-20th century use single-pipe systems that collect both sewage and urban runoff from streets, roofs and other impervious surfaces. This type of collection system is referred to as a combined sewer system. During storms, the flow capacity of the sewers may be exceeded and the overflow discharged into a receiving water body (RWB) through spillways without any control and remediation. Combined sewer overflows (CSOs) may, therefore, produce serious water pollution and flooding problems in downstream RWBs. Methodologies for a rational management of CSOs quantity and quality share many commonalities, and these two aspects should be considered together in order to maximize benefits and promote local distributed actions, especially in high urban density areas where the space availability for the construction of CSO storage tanks is often a limiting factor. In this paper, a novel strategy to control downstream flow propagation of a CSO as well as to improve its quality is tested on a real case study in the area of the metropolitan city of Milan. The approach is based on the combination of grey, green and blue infrastructures and exploits the integrated storage and self-depuration capacities of a firstflush tank, a constructed wetland and a natural stream to obtain admissible flow rates and adequate water quality in the RWB. The results, evaluated through a modelling framework based on simplified equations of water and pollutants dynamics, show excellent performances for the integrated system, both in terms of flow control and pollution mitigation. The pollution, using biological oxygen demand concentration as a proxy of the whole load, was decreased by more than 90% and downstream flooding situations were avoided, despite the spillway was not regulated. Concerning the economic point of view, from a rough estimate of the costs, the system allows reducing the investment of 30 to 50% in respect to the traditional CSO controls based solely on flow detention tanks. The proposed approach, as well as the modelling framework for its effective implementation, appear strongly scalable in different world contexts and aim to fill the gap between urban and rural environments in the management of stormwater and CSOs, promoting the involvement of the water managers, the irrigation-reclamation agencies and regional authorities.