This paper examines the links between neoliberal urbanism and disaster vulnerability in Cartagena, a town on the Chilean central coast. In recent decades, this area has been transformed by speculative urban development, resulting in environmental damage and increased socio-economic segregation. We adopt a political ecology perspective to consider how these changes interact with disaster risk, drawing on ten interviews with representatives of local community organisations, a collaborative mapping exercise and census data. We find that mass tourism and informal urban expansion contribute to environmental degradation, as well as infrastructural and economic fragility, leading to increased risks for residents and tourists alike. We position our case study against the critiques of vulnerability leveraged by several critical geographers, who have come to see the term as depoliticising. While sympathising with these critiques, we argue for the usefulness of vulnerability analyses combining political ecology approaches to the study of human-nature relations and insight from critical urban studies on issues such as neoliberal planning policies, extractivism, urban informality and touristification. Articulated in these terms, vulnerability can be usefully mobilised to push for substantive policy change.