Background <p>N7-methylguanosine (m7G) modifications have been proved to be related to tumor progression and development. Signatures based on m7G-related genes (MRGs) can predict prognosis and therapeutic response in a diversity of tumors. Nevertheless, further investigation is required to understand the precise role of MRGs in triple-negative breast cancer (TNBC).</p> Methods <p>Consensus clustering was used to identify MRGs clusters, and a signature was developed using a least absolute shrinkage and selection operator (LASSO) and Cox by utilizing the prognostic differentially expressed genes (DEGs) found across the clusters. To demonstrate the accuracy of the signature, ROC analysis was performed. RT-qPCR was used to identify the expression of genes associated with risk. Afterward, we developed a nomogram to enhance the effectiveness of our predictive instrument in clinical settings, and PCR and gene functional validation experiments were conducted. We assessed immune checkpoint markers and immune cell infiltration by IHC and flow cytometry, respectively, and validated prognostic utility in a clinical cohort.</p> Results <p>The MRGs signature, consisting of six genes, was constructed and was confirmed to be closely correlated with the prognosis of TNBC patients. In comparison to the predictive accuracy of the other individual predictors, we found that this MRGs signature performs better obviously. Furthermore, the ImmunoScores exhibited higher levels in the low-risk category. Reduced CD8 + T-cell density and PD-L1 expression in high-risk patients were consistent with an immunosuppressive phenotype and predicted poorer prognosis. Overexpression of CLEC2D inhibited the proliferation, migration, and invasion of TNBC.</p> Conclusions <p>The MRGs’ signature could function as a predictor of prognosis and provide a reference of great significance for individual therapy of TNBC.</p>