The dispensation of medicines in some low- and middle-income countries is often carried out by private vendors operating under constrained conditions. The aim of this study was to understand the challenges reported by employees of dispensaries, specifically, chemical and herbal shops and pharmacies in Accra, Ghana. Our objectives were twofold: (1) to assess challenges faced by medicine vendors related to dispensing antimicrobials (antibiotic and antimalarial medications), and (2) to identify opportunities for improving their stewardship of antimicrobials. Data were collected in 79 dispensaries throughout Accra, in 2021, using a survey questionnaire. We used open-ended questions, grounded on an adapted socioecological model of public health, to analyze these data and determine challenges faced by respondents. We identified multiple, interlocking challenges faced by medicine vendors. Many of these relate to challenges of antimicrobial stewardship (following evidence-based practices when dispensing medicines). Overall, medicine vendors frequently reported challenges at the Customer and Community levels. These included strained interactions with customers and the prohibitive costs of medications. The consequences of these challenges reverberated and manifested through all levels of the socioecological model of public health (Entity, Customer, Community, Global). The safe and effective distribution of medications was truncated by strained interactions, often related to the cost of medicines and gaps in knowledge. While addressing these challenges requires multifaceted approaches, we identified several areas that, if intervened upon, could unlock the great potential of antimicrobal stewardship. The effective and efficient implementation of key interventions could facilitate efforts spearheaded by medicine vendors and leverage the benefits of their role as health educators and service providers. Addressing barriers faced by medicine vendors would provide an opportunity to significantly improve the provision of medications, and ultimately population health. Such efforts will likely expand access to populations who may otherwise be unable to access medications and treatment in formal institutions of care such as hospitals. Our findings also highlight the broad range of care provided by shopkeepers and vendors at dispensaries. These findings suggest that the meaningful engagement of dispensaries as valued conduits of community health is a promising pathway for interventions aiming to improve antimicrobial stewardship.