This paper proposes a stigma-vulnerability nexus as a critical incursion into understandings of and responses to drug-related social problems. Considering stigma and vulnerability as sites of ostensibly empathetic interventions that aim to mitigate the impact of illicit substances, it proposes that the two concepts are best deployed when located within the political economy of drug harms. Doing so foregrounds the material inequalities resulting from existing socio-economic arrangements and highlights the limitations of them being politically mobilised in purely cultural-interactional ways, which can serve to overlook structural conditions and justify harmful political choices. As a theoretical perspective, the stigma-vulnerability nexus is therefore concerned with the macro-structural factors that shape both concepts and how they intersect. To demonstrate its value as an analytic tool, it is first applied to the framing of ‘County Lines’ dealing, where senior gang members are stigmatised, but the wider drivers of vulnerability among the young people they exploit are overlooked. Secondly, the nexus is applied to the case of new psychoactive substances. Here, the perceived vulnerability of young people is used to justify responses that ultimately lead to amplified harms being displaced onto structurally disadvantaged populations such as the homeless and prison inmates, compounding their economic vulnerability and class stigma