Flooding causes serious impacts on the old town of Venice, its residents, and its cultural heritage. Despite this existence-defining condition, limited scientific knowledge on flood risk of the old town of Venice is available to support decisions to mitigate existing and future flood impacts. Therefore, this study proposes a risk assessment framework to provide a methodical and flexible instrument for decision-making for flood risk management in Venice. We first use a state-of-the-art hydrodynamic urban model to identify the hazard characteristics inside the city of Venice. Exposure, vulnerability, and corresponding damage are then modeled by a multi-parametric, micro-scale damage model which is adapted to the specific context of Venice with its dense urban structure and high risk awareness. Furthermore, a set of individual protection scenarios are implemented to account for possible variability in flood preparedness of the residents. This developed risk assessment framework was tested for the flood event of 12 November 2019 and proved able to reproduce flood characteristics and resulting damage well. A scenario analysis based on a meteorological event like 12 November 2019 was conducted to derive flood damage estimates for the year 2060 for a set of sea level rise scenarios in combination with a (partially) functioning storm surge barrier, the Modulo Sperimentale Elettromeccanico (MOSE). The analysis suggests that a functioning MOSE barrier could prevent flood damage for the considered storm event and sea level scenarios almost entirely. A partially closed MOSE barrier (open Lido inlet) could reduce the damage by up to 34 % for optimistic sea level rise prognoses. However, damage could be 10 % to 600 % higher in 2060 compared to 2019 for a partial closure of the storm surge barrier, depending on different levels of individual protection.