The NCI’s Cancer Center Cessation Initiative (C3I) has a specific objective of helping cancer centers develop and implement sustainable programs to routinely address tobacco cessation with patients. Sustaining tobacco treatment programs requires the maintenance of (1) core program components, (2) ongoing implementation strategies, and (3) program outcomes evaluation. NCI funding of C3I included a commitment of resources toward sustainability. This article presents case studies to illustrate key strategies in developing sustainability capacity across 4 C3I-funded sites. Case studies are organized according to the domains of sustainability capacity defined in the Clinical Sustainability Assessment Tool (CSAT). We also describe the C3I Sustainability Working Group agenda to make scientific and practical contributions in 3 areas: (1) demonstrating the value of tobacco use treatment in cancer care, (2) identifying implementation strategies to support sustainability, and (3) providing evidence to inform policy changes that support the prioritization and financing of tobacco use treatment. By advancing this agenda, the Sustainability Working Group can play an active role in advancing and disseminating knowledge for tobacco treatment program sustainability to assist cancer care organizations in addressing tobacco use by patients with cancer within and beyond C3I.