In this article, we suggest rethinking how to move forward in a way that better elucidates socio-economic and political factors driving inequities, and in turn points to more broad sweeping, deep-rooted changes necessary if pandemics in the future are finally going to be mitigated pre-emptively rather than reactively. To this end, we argue that a more comprehensive, flexible and incisive approach is necessary – a hermeneutic framework that focuses analytical attention and action on interventions upstream, on the multifaceted interrelations necessary before lives currently deemed disposable are lost. Unlike dominant public health and epidemiological approaches, that is, Social Determinants of Health and Syndemics, proven unlikely to fuel structural change or to enable pre-emptive response, we propose the framework of pathogenicity and apply it to urban contexts to answer questions concerning the relationship between microbes on the one hand, and on the other, the urban, social, political, ideological, global, scientific, economic and many other relations that galvanise these into pathogens. By employing pathogenicity in the context of two case studies in the US and Turkey, we shift emphasis away from tackling microbes to better understanding what makes those microbes, and even the interventions implemented to stop them, so destructive.