Empirical evidence of increasing flood damages and the prospect of climatic change has initiated discussions in the flood management community on how to effectively manage flood risks. In the Netherlands, the framework of multi-layer safety (MLS) has been introduced to support this risk-based approach. The MLS framework consists of three layers: (i) prevention, (ii) spatial planning and (iii) evacuation. This paper presents a methodology to evaluate measures in the second layer, such as wet proofing, dry proofing or elevating buildings. The methodology uses detailed land-use data for the area around the city of Rotterdam (up to building level) that has recently become available. The vulnerability of these detailed land-use classes to flooding is assessed using the stage–damage curves from different international models. The methodology is demonstrated using a case study in the unembanked area of Rotterdam in the Netherlands, as measures from the second layer may be particularly effective there. The results show that the flood risk in the region is considerable: EUR 36 million p.a. A large part (almost 60 %) of this risk results from industrial land use, emphasising the need to give this category more attention in flood risk assessments. It was found that building level measures could substantially reduce flood risks in the region because of the relatively low inundation levels of buildings. Risk to residential buildings would be reduced by 40 % if all buildings would be wet-proofed, by 89 % if all buildings would be dry-proofed and elevating buildings over 100 cm would render the risk almost zero. While climate change could double the risk in 2100, such building level measures could easily nullify this effect. Despite the high potential of such measures, actual implementation is still limited. This is partly caused by the lack of knowledge regarding these measures by most Dutch companies and the legal impossibility for municipalities to enforce most of these measures as they would go beyond the building codes established at the national level.