Climate change has led to the increased intensity and frequency of extreme meteorological events, threatening the drainage capacity in urban catchments and densely built-up cities. To alleviate urban flooding disasters, strategies coupled with green and grey infrastructure have been proposed to support urban stormwater management. However, most strategies rely largely on diachronic rainfall data and ignore long-term climate change impacts. This study described a novel framework to assess and to identify the optimal solution in response to uncertainties following climate change. The assessment framework consists of three components: (1) assess and process climate data to generate long-term time series of meteorological parameters under different climate conditions; (2) optimise the design of Grey-Green infrastructure systems to establish the optimal design solutions; and (3) perform a multi-criteria assessment of economic and hydrological performance to support decision-making. A case study in Guangzhou, China was carried out to demonstrate the usability and application processes of the framework. The results of the case study illustrated that the optimised Grey-Green infrastructure could save life cycle costs and reduce total outflow (56-66%), peak flow (22-85%), and TSS (more than 60%) compared to the fully centralised grey infrastructure system, indicating its high superior in economic competitiveness and hydrological performance under climate uncertainties. In terms of spatial configuration, the contribution of green infrastructure appeared not as critical as the adoption of decentralisation of the drainage networks. Furthermore, under extreme drought scenarios, the decentralised infrastructure system exhibited an exceptionally high degree of removal performance for non-point source pollutants.