Recent studies on women’s substance use have emphasized the role of structural and environmental contexts in shaping substance use patterns and harms, but the dynamics constitutive of specific substance use contexts are seldom unpacked. This study works with Cameron Duff’s elaboration of context as an assemblage of space, embodiment and practice to explore the contextual dynamics that mediate substance use practices among socially marginalized women. In-depth interviews were used to gather data from a purposive sample of street-involved women who use drugs ( n = 16) in Uyo, Nigeria. Data revealed that substance use was mediated by actors, social norms and processes within social networks developed in street environments. The women used substances to achieve particular affective states such as pleasure, stress relief and coping with trauma. Social network dynamics combined with the use of drugs to manage trauma and social stress, within a wider context of social and material deprivations, to foster substance use practices that created risk for harm. Drug harms were not inherent to the substance use experience or incidental to benefits and pleasures. Instead, they were unintended, but inevitable, outcomes of the embodied practices of beneficial substance use. On the other hand, corporeal techniques of controlled drug use served to minimize drug harms. Findings indicate a need to address the contextual dynamics that influence harmful patterns of substance use, and to leverage the harm reducing potentials of controlled use practices.