Tools exist to predict fatalities related to floods, but current models do not focus on fatalities in buildings. For example, Storm Xynthia in France in 2010 resulted in 41 drowning deaths inside buildings. Therefore, there has been increasing recognition of the risk of people becoming trapped in buildings during floods. To identify buildings which could expose their occupants to a risk of death in the case of flooding, we propose the use of the extreme vulnerability index (VIE index), which identifies which buildings are at greatest risk of trapping people during floods. In addition, the “mortality function method” is used to further estimate the expected number of fatalities based on (1) groups of vulnerable people (e.g., aged or disabled), (2) the location of buildings in relation to major watercourses, and (3) the configuration of buildings (e.g., single or multiple entries and single or multiple stories). The overall framework is derived from case studies from Storm Xynthia which give a deterministic approach for deaths inside buildings for coastal floods, which is suited for low-lying areas protected by walls or sandy barriers. This methodology provides a tool which could help make decisions for adaptation strategy implementation to preserve human life.