BACKGROUND: The efficacy of radiotherapy to the internal mammary node (IMN-RT) and axillary lymph node regions (ALRT) in enhancing disease-free survival (DFS) among patients with breast cancer (BC) in the context of contemporary systemic chemotherapy has not been clearly established. METHODS: This retrospective study included 512 patients with BC who underwent primary breast surgery and regional nodal irradiation between 2008 and 2014. The patient cohort was divided into 160 early-stage (T1-T2, N0-N1) and 352 locally advanced-stage (T3-T4, N2-N3) cases. We employed Kaplan-Meier survival analysis to calculate locoregional recurrence-free survival (LRFS), DFS, and overall survival (OS). A propensity score-matched (PSM) analysis was performed for patients who received IMN-RT. RESULTS: A high proportion of patients (95.9%) received adjuvant chemotherapy and 89.8% received taxane-based regimens. All HER2-positive patients were treated with anti-HER2 therapy, and hormone therapy was administered to 97.5% of the patients with ER-positive tumors. While all patients underwent supraclavicular fossa RT, only 20 patients (3.9%) received additional IMN-RT. ER-negative/HER2-negative patients demonstrated a significantly lower 10-year DFS (p = 0.036) and OS (p = 0.006). PSM analysis showed that there were no differences in LRFS (p = 0.308) and DFS (p = 0.388) between patients receiving IMN-RT and those who did not. For pathological N3 patients, the 10-year LRFS (67% vs. 81.7%, p = 0.153) and DFS (62.3% vs. 64.9%, p = 0.789) rates were similar between those who underwent ALRT and those without ALRT. CONCLUSION: In the modern era of systemic therapy, RT to the IMN or axilla does not substantially improve the clinical outcomes in patients with LN-positive early- or locally advanced-stage BC.