Background <p>Dysregulated <i>FGFR4</i> signaling has been associated with aggressive subtypes of breast cancers, characterized by HER2 enrichment or endocrine resistance. However, the biological functions of <i>FGFR4</i> across breast cancer subtypes remain unclear. This study investigated the molecular characteristics of <i>FGFR4</i>-high tumors to inform potential therapeutic strategies.</p> Methods <p>This study analyzed clinicopathological characteristics and gene expression profile of 53 hormone receptor-positive (HR⁺) and 41 HR-negative (HR⁻) patients using the AmoyDx Master Panel. The results were validated using The Cancer Genome Atlas (TCGA) and single-cell RNA-seq datasets.</p> Results <p>The patients in the PUMCH cohort (n = 94) were stratified by HER2 and HR statuses and further stratified according to <i>FGFR4</i> expression. <i>FGFR4</i>-high tumors showed no genomic differences but enriched immune activation pathways, specifically in HR⁺HER2-low/positive subgroups. HR⁺ tumors with co-expression of <i>FGFR4</i> and HER2 exhibited increased immune infiltration (T cells, NK cells, M1 macrophages) and upregulated checkpoints (<i>BTLA, CTLA4, HAVCR2, LAG3</i>). Single-cell data confirmed elevated T-cell abundance in HR⁺HER2-high FGFR4-high cases. TCGA analysis linked high <i>FGFR4</i> to prolonged disease-free survival (DFS) in HR⁺HER2-positive patients but reduced DFS in HR⁺HER2-zero patients.</p> Conclusions <p>Co-expression of <i>FGFR4</i> and HER2 is associated with a proinflammatory tumor microenvironment in HR⁺ breast cancer, suggesting immunotherapy potential. Further studies should explore therapeutic strategies to reshape the tumor immune microenvironment.</p>