Current design philosophies are not always able to guarantee the robustness of buildings, especially when extreme events cause initial failures for which alternative load paths cannot be effective. Fuse-based segmentation has the potential to address this shortcoming, by isolating collapse when its initiation is inevitable. However, no study has yet been performed to clarify under which conditions and in which contexts it can be a suitable solution to mitigate the risk of disproportionate building collapse. Most applicable frameworks for performing risk-based cost-benefit assessments cannot be directly applied to study fuse-based segmentation since they rely on overly simplified structural models that cannot represent collapse propagation phenomena. In this article, a scenario-based methodology is proposed for evaluating the cost-effectiveness of fuse-based segmentation. The proposed methodology was also applied to a case-study consisting of a six-storey reinforced concrete building, revealing that there are a wide range of contexts for which fuse-based segmentation can be cost-effective for this type of structure.