Neoadjuvant systemic therapy (NST) has transformed the surgical management of breast cancer, providing a means of tumour downstaging that increases eligibility for breast-conservation surgery (BCS). For patients initially considered ineligible for BCS due to large tumour size or unfavourable tumour-to-breast volume ratios, NST has demonstrated the potential to convert mastectomy candidates to lumpectomy candidates. Multiple clinical trials have shown BCS conversion rates as high as 75% following NST, especially in aggressive subtypes such as triple-negative and HER2-positive breast cancers. Importantly, long-term oncologic outcomes—including local recurrence and survival—remain comparable between patients receiving NST followed by BCS and those undergoing upfront surgery. Accurate pre- and post-treatment assessment of disease extent is crucial and is primarily achieved by magnetic resonance imaging. Precise localization of the original tumour site, often marked with a biopsy clip prior to NST, guides adequate resection at the time of surgery. Modern localization techniques, such as radioactive or magnetic seeds, have shown improved workflow and patient comfort compared to traditional wire-guided approaches. The extent of surgical excision is influenced by residual calcifications and clip placement, though the achievement of negative margins—defined as ‘no ink on tumor’—remains the accepted standard in patients who underwent NST. This chapter explores the current rationale and updated supporting evidence for NST in promoting BCS, outlines imaging and localization strategies, and discusses considerations critical to ensuring oncologic safety and surgical success in this evolving treatment paradigm.