Wastewater treatment plants (WWTPs) are among the most important infrastructures, especially in coastal cities with a risk of flooding. During intense floods, runoff volume may exceed the capacity of a WWTP causing plant failures. This paper investigates the impacts of flooding on combined sewer overflows (CSOs) in a WWTP in New York City. The impacts of CSOs after flooding are classified into four terms of health, economic, social, and environmental factors. Different factors are defined to evaluate impacts of CSOs using multi-criteria decision-making of Preference Ranking Organization Method For Enrichment Evaluation and fuzzy technique for order performance by similarity to ideal solution. Since volume and depth were found the most significant factors for the CSO impact assessment, the Gridded Surface Subsurface Hydrologic Analysis model was run to compute flood depth and CSO volume under three treatment plant failure scenarios considering the hurricane Sandy information. Sensitivity analysis revealed that the TSS, BOD, and dissolved oxygen have the highest impacts on CSO. Uncertainty analysis was applied to investigate CSO impact variation. Results show that evaluating the impacts of CSOs in different aspects can give a good idea for flood planning and management with higher efficiency during storms.