Tissue-resident memory T (T_RM) cells are a distinct subset of memory T cells that reside in non-lymphoid tissues for prolonged periods of time without significant recirculation providing continued immune surveillance at these sites. Recent studies suggest that T_RM cells are also enriched within tumor tissue. Expression of inhibitory immune checkpoints (ICPs) is particularly enriched on this subset of tumor-infiltrating T cells, suggesting that they are major targets for newer therapies targeting ICPs such as the programmed death-1 pathway. Recent studies suggest that tissue restriction of these cells without recirculation may also lead to heterogeneity of T_RM cells within individual metastatic lesions, ultimately leading to inter-lesional diversity. Thus, individual metastatic lesions may contain genomically distinct immune microenvironments that impact both evolution of tumors as well as the mechanisms underlying response and resistance to immune therapies. Understanding the biology of T_RM cells infiltrating tumors will be essential to improving immune-based approaches in diverse settings.