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The increasing use of neoadjuvant systemic therapy (NAC) has led to a significant paradigm shift in the locoregional treatment of breast cancer, with increasing emphasis on response-guided de-escalation. In current practice, both clinical and pathologic responses to treatment are being leveraged to minimize the extent and morbidity of local therapy while maintaining oncologic safety. In patients presenting with clinically node-negative (cN0) disease and high-risk biologic subtypes, sentinel lymph node biopsy (SLNB) omission after NAC is an area of evolving interest. For those presenting with clinically node-positive disease (cN+) yet who attain a pathologic complete response (pCR) in the lymph nodes after NAC, emerging evidence suggests that SLNB alone with omission of regional nodal irradiation (RNI) may be considered. Ongoing trials are evaluating whether cN+ patients with residual micrometastases or macrometastases after NAC may also be treated with SLNB alone, using RNI in lieu of axillary lymph node dissection to achieve adequate locoregional control. Parallel advances in radiation therapy (RT) are reshaping treatment decisions and sequencing, including when to deliver agents concurrently with radiation and when to hold them. Exceptional responders who attain a breast pCR and undergo breast conservation may have little or no residual tumor bed to justify tumor bed boost, and several trials are assessing the safety of radiation omission in these subgroups. Finally, premastectomy RT is being explored as a strategy to facilitate immediate breast reconstruction while avoiding radiation-related complications. Together, these developments highlight a shift toward individualized, response-adapted locoregional management in early-stage breast cancer.