<p>SIRT7, one of the least studied members of the Sirtuins family, is an NAD⁺-dependent lysine deacetylase and desuccinylase. While previous studies using affinity enrichment and quantitative proteomics identified numerous lysine-deacetylated substrates of SIRT7, its lysine-desuccinylated substrates remain underexplored, limiting our understanding of its role in cellular homeostasis. Here, we demonstrated that SIRT7 is predominantly expressed in immune tissues, especially in adaptive immune cells, including T cells. Through proteomics, lysine succinylome, and acetylome analysis of spleen from wild-type (WT) and <i>Sirt7</i>^{<i>−/−</i>} mice, we identified significant succinylation of proteins involved in the branched-chain amino acid (BCAA) catabolism pathway in <i>Sirt7</i>^{<i>−/−</i>} mice. We further found that SIRT7 partially localizes to mitochondria, interacting with key enzymes of the BCAA catabolism pathway and promoting their desuccinylation. <i>Sirt7</i> deficiency leads to enhanced BCAA catabolism, accumulation of acyl-CoA, and increased fatty acid (FA) synthesis. As T cells rely heavily on amino acid metabolism for activation, differentiation, and function, we investigated the impact of SIRT7 using a T cell-specific <i>Sirt7</i> knockout mouse model (<i>Sirt7</i>^<i>fl/fl</i><i>Cd4</i>-Cre). Our results show that SIRT7 is crucial for T cell proliferation, activation, and antitumor function. <i>Sirt7</i> deficiency in T cells results in the accumulation of BCAA metabolites and FAs, reduced cytotoxic cytokines secretion such as IFN-γ, and T cell exhaustion. Reducing BCAA levels with BT2, a BCKDK inhibitor, or BCAA-free treatment alleviated these effects, while FA treatment exacerbates them. Overall, our findings identify SIRT7 as a critical regulator linking BCAA and FA metabolism to T cell antitumor immunity, providing new insights into its potential as a therapeutic target.</p>