Tissue resident memory T (TRM) cells are preferentially localised at the site of primary infection and in many cases are defined by the expression of the cell surface markers CD69 and CD103. Gene expression analysis has shown that TRM cells in multiple tissues share a core transcriptome, characterised by the downregulation of a repertoire of pro-migratory genes, aiding retention. Although cytokines such as TGF-β and IL-15 have been proposed to promote TRM cell development, it is clear that there are tissue-specific determinants of TRM cell development and maintenance that remain elusive. By developing a novel methodology to generate TRM-like cells in vitro, we identify a critical role for retinoic acid (RA) and the transcriptional repressor Hypermethylated in Cancer 1 (HIC1) in the development of TRM-like cells. Transcriptomic analysis revealed that activation of CD8+ T cells in the presence of IL-2, IL-15, TGF-β and RA resulted in faithful expression and repression of the core TRM cell transcriptome, and that HIC1 was critical in regulating repression of the core gene program. Critically, we find that RA, TGF-β and RA/TGF-β conditions induce unique gene signatures that have similarities to bona fide TRM cells from the gut, liver or lung, providing a unique insight into the factors that potentially regulate tissue-specific TRM cell development. As TRM cells are key mediators of immunity in recurrent infections and cancer, but are capable of facilitating autoimmune disease when dysregulated, understanding how best to modulate these cells will be crucial in informing the design of novel therapeutics.