Despite the high tobacco use rates (~80%) and tobacco-related cancers being the second leading cause of death among people experiencing homelessness within the United States, these individuals rarely receive tobacco use treatment from homeless-serving agencies (HSAs). This qualitative study explored the enablers and inhibitors of implementing an evidence-based tobacco-free workplace (TFW) program offering TFW policy adoption, specialized provider training to treat tobacco use, and nicotine replacement therapy (NRT) within HSAs. Pre- and post-implementation interviews with providers and managers (n = 13) pursued adapting interventions to specific HSAs and assessed the program success, respectively. The organizational readiness for change theory framed the data content analysis, yielding three categories: change commitment, change efficacy and contextual factors. Pre- to post-implementation, increasing challenges impacted the organizational capacity and providers’ attitudes, wherein previously enabling factors were reframed as inhibiting, resulting in limited implementation despite resource provision. These findings indicate that low-resourced HSAs require additional support and guidance to overcome infrastructure challenges and build the capacity needed to implement a TFW program. This study’s findings can guide future TFW program interventions, enable identification of agencies that are well-positioned to adopt such programs, and facilitate capacity-building efforts to ensure their successful participation.