Background <p>Luminal breast cancer has a high incidence and significant heterogeneity. Exosomes, as key mediators of intercellular communication, are involved in the tumor process, but the related genes in Luminal breast cancer regarding prognosis and mechanism remain unclear.</p> Methods <p>This study integrated a total of 1251 Luminal breast cancer samples from the TCGA and GEO databases. Differential expression analysis and Cox regression were used to screen out prognostic-related exosomal genes, and a multivariate Cox risk prognostic model was constructed. Kaplan-Meier survival analysis and time-dependent ROC curves were used to evaluate the model performance. Further immunological analysis, gene set enrichment analysis (GSEA), transcription factor/ceRNA regulatory network construction, and drug sensitivity analysis were conducted. Results: A total of 4 prognostic-related exosomal genes (LCN2, RRAS2, LRG1, LTF) were identified. Based on this, a risk model was constructed that can effectively distinguish high-risk and low-risk patients, and the overall survival of the high-risk group was significantly shorter. Immunological analysis showed that the high-risk group had increased M2 Macrophage infiltration and accompanied by immune function inhibition. GSEA suggested that the high-risk group was enriched in tumor progression-related pathways such as DNA replication and homologous recombination. Drug sensitivity analysis indicated that the high-risk group showed higher sensitivity to PI3K inhibitors and chemotherapy drugs.</p> Conclusion <p>LCN2, RRAS2, LRG1, and LTF can be used as prognostic markers for Luminal breast cancer, related to immune suppression and tumor progression, and the high-risk group is more sensitive to PI3K inhibitors and chemotherapy drugs, providing potential targets for precision treatment.</p>