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Antimicrobial resistance (AMR) continues to present a significant public health challenge globally. Antimicrobial Stewardship Programs (ASPs) are key in optimizing antibiotic use and mitigating AMR’s impact. This study explores the factors influencing the implementation of ASPs in three Dar es Salaam Regional Referral Hospitals (RRHs).We explored the facilitators and barriers for the implementation of ASPsin Dar es Salaam’s RRH in Tanzania.Eleven purposively selected medical professionals from three RRHs participated in key informant interviews for this study, which employed an exploratory qualitative case study design. The audio recordings of the interviews were verbatim transcribed, and thematic analysis as proposed by Braun and Clarke (2006) was applied for analysis.Two major themes were unveiled in this study: barriers to implementation of ASPs and the facilitators to implementation of ASPs. Resource constraints, staff shortage, inconsistency in adherence to guidelines, reluctance to change among staff, and logistical challenges in procurement of program consumables were highlighted as the barriers to implementing ASP. Leadership support, access to ASP resources through partnerships, and ASP-specific training and capacity-building initiatives were the major facilitators for implementing ASPs.The implementation of ASPs in Dar es salaam RRHs has established a foundational practice necessary to combat AMR. The study demonstrated the role of capacity building and institutional support in implementing these programs. Despite the benefits, these programs are challenged by systemic and behavioral limitations. While the programs show potential, their success remains fragile and dependent on addressing these critical, deeply ingrained systemic issues. Thus, the Ministry of Health should provide dedicated domestic funding and strengthen national governance structures to guide, coordinate, and monitor ASP implementation across facilities, and at the hospital level, ASPs must be integrated with existing programs especially IPC with clear performance indicators, routine reporting, and targeted investments such as rapid diagnostics and standardized training to address operational and behavioral barriers.