In this Oncology Nursing News Case-Based Peer Perspectives program, NP Theresa Stukus and NP Nelli Zafman discuss the evolving frontline management of metastatic triple-negative breast cancer (mTNBC), highlighting how recent advances in antibody-drug conjugates (ADCs) are reshaping treatment strategies. Through a series of realistic clinical scenarios, the faculty examine evidence-based approaches to frontline treatment selection, emphasizing the importance of comprehensive biomarker testing, individualized treatment planning, and shared decision-making based on patient characteristics, disease burden, and quality-of-life considerations. The discussion also explores practical management of treatment-related adverse events, including gastrointestinal, hematologic, ocular, and oral toxicities, while outlining proactive monitoring, patient education, and supportive care strategies that help patients remain on therapy. Throughout the program, the speakers underscore the critical role of oncology nurse practitioners and the multidisciplinary care team in optimizing outcomes, implementing emerging clinical evidence into routine practice, and supporting patients throughout their metastatic triple-negative breast cancer treatment journey.