Current understanding of T-box transcription factors T-bet and Eomes in murine NK cells and ILCs are primarily restricted to their role during development. Our recent studies have shown that T-bet and Eomes are required for the homeostasis, function, and identity of human NK cells using CRISPR/Cas-9 loss-of-function in primary human NK cells (PMID: 37279078). However, the in-vivo study of human NK cells was limited to xenograft models that do not recapitulate an intact species-matched immune environment. To better understand T-bet’s role in mature murine NK cells in vivo, we generated an inducible NKp46 (Ncr1)-specific T-bet floxed knock-out mouse (Ncr1-Tbx21^-/-) model and investigated differential requirement for T-bet in NK cells and ILCs across different tissues. Ncr1-Tbx21^-/- mice had significantly reduced stage IV NK cells in the spleen, blood, and lung due to increased apoptosis. However, NK cells were not impacted in the bone marrow, lymph nodes, liver and SI lamina propria. In contrast, the number of liver ILC1s and SI lamina propria ILC3s were significantly reduced in Ncr1-Tbx21^-/- mice. Liver ILC1s had marked transcriptional changes upon induced T-bet deletion, indicating a key ongoing regulation by T-bet. Thus, sustained T-bet expression is required for homeostasis and maintenance of these ILC types. We also investigated the redundant functions of T-bet and Eomes by generating Ncr1-Tbx21^-/-Eomes^-/- mice. Upon Cre-mediated deletion of T-bet and Eomes, there was a rapid loss of NK cells in spleen and blood due to apoptosis, which was markedly greater than individual T-bet and Eomes deletion. Lastly, we examined the T-bet and Eomes contribution to NK cells and ILC1 during murine cytomegalovirus (MCMV) infection. T-bet (and ILC1s) were dispensable, while Eomes (and NK cells) were critical, for host protection against MCMV. These findings reveal novel tissue-specific regulation by specific T-box TFs in NKp46⁺ ILCs during homeostasis and response to viral infection.