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Background: Against the backdrop of North America’s overdose crisis, most overdose deaths are occurring in housing environments, largely due to individuals using drugs alone. Overdose deaths in cities remain concentrated in marginal housing environments (e.g., single-room occupancy housing, shelters), which are often the only forms of housing available to urban poor and drug-using communities. This commentary aims to highlight current housing-based overdose prevention interventions and to situate them within the broader environmental contexts of marginal housing. In doing so, it calls attention to the need to better understand marginal housing as sites of overdose vulnerability and public health intervention to optimize responses to the overdose crisis. Conclusion: Emerging housing-focused interventions are designed to address key drivers of overdose risk (e.g., using alone, toxic drug supply). Yet, broader contextual factors (e.g., drug criminalization, housing quality, gender) are equally critical factors that shape how structurally vulnerable people who use drugs navigate and engage with harm reduction interventions. A more comprehensive understanding of these contextual factors within housing environments is needed to inform policy and programmatic interventions that are responsive to the needs of people who use drugs in these settings.