As a consequence of climate change and urbanization, many cities will have to deal with more flooding and extreme heat stress. This paper presents a framework to maximize the effectiveness of Nature-Based Solutions (NBS) for flood risk reduction and thermal comfort enhancement. The framework involves an assessment of hazards with the use of models and field measurements. It also detects suitable implementation sites for NBS and quantifies their effectiveness for thermal comfort enhancement and flood risk reduction. The framework was applied in a densely urbanized study area, for which different small-scale urban NBS and their potential locations for implementation were assessed. The overall results show that the most effective performance in terms of flood mitigation and thermal comfort enhancement is likely achieved by applying a range of different measures at different locations. Therefore, the work presented here shows the potential of the framework to achieve an effective combination of measures and their locations, which was demonstrated on the case of the Sukhumvit area in Bangkok (Thailand). This can be particularly suitable for assessing and planning flood mitigation measures in combination with heat stress reduction.