Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and HER2/neu expression, making it unresponsive to hormonal and HER2-targeted therapies. ID4, an inhibitor of differentiation protein, plays a crucial role in the reprogramming of mammary cells by regulating the transcription of lineage-specific genes. This study investigates ID4’s potential to reprogram TN tumors into luminal tumors, making them sensitive to endocrine treatments. Methods: In-silico analyses evaluated ID4 expression in human TN tumors using public datasets. In vitro experiments on MDA-MB231 ER- breast cancer cell lines involved silencing ID4 using CRISPR-Cas9 or inhibiting it with AGX51. Gene and protein expression were analyzed via RT-qPCR and Western blot. Phenotypic changes were assessed using colony formation, migration, and wound healing assays. Cells were treated with Tamoxifen to evaluate endocrine response. Results: In-silico analysis stratifying ID4 expression in TN tumors into “high” and “low” groups revealed distinct luminal and basal gene expression patterns. The low ID4 group had increased luminal (p<0.05) and decreased basal signatures (p<0.01). Gene set enrichment analysis indicated enrichment of “estrogen response late and early” hallmarks. In vitro experiments confirmed a significant increase in ER and GATA3 expression and a decrease in EGFR expression (p<0.05) upon ID4 silencing, which also significantly reduced cell proliferation, migration, colony formation (p<0.05), and tumor size in an in vivo model (p<0.01). Tamoxifen treatment significantly decreased proliferation and migration in silenced cells (p<0.05). Treatment with AGX51 significantly reduced tumor size in an in vivo model (p<0.01). Conclusions: Our results highlight ID4’s influence on estrogen pathways and TNBC traits, suggesting ID4 targeting as a new treatment approach.