CD8 tissue-resident memory T (T ) cells primarily reside in nonlymphoid tissues without recirculating and provide front-line protective immunity against infections and cancers. CD8 T cells can be generally divided into CD69 CD103 T cells (referred to as CD103 T cells) and CD69 CD103 T cells (referred to as CD103 T cells). TGF-β plays a critical role in the development and maintenance of CD103 CD8 T cells. In this review, we summarize the current understanding of tissue-specific activation of TGF-β mediated by integrins and how it contributes to CD103 CD8 T cell development and maintenance. Furthermore, we discuss the underlying mechanisms utilized by TGF-β to regulate the development and maintenance of CD103 CD8 T cells. Overall, this review highlights the importance of TGF-β in regulating this unique subset of memory CD8 T cells that may shed light on improving vaccine design to target this population.