This chapter provides a comprehensive and in-depth discussion of the systemic treatmet strategies for metastatic nasopharyngeal carcinoma (mNPC), detailing the development and refinement of approaches based on current clinical evidence. It traces the development of chemotherapy regimens, highlighting gemcitabine plus cisplatin as the established first-line standard. The discussion extends to targeted therapies, with particular attention to agents against the EGFR and VEGF pathways, as well as the increasing application of immune checkpoint inhibitors, especially in combination with chemotherapy. The chapter also examines the incorporation of local treatments and maintenance strategies into systemic approaches, emphasizing the role of multidisciplinary care in improving outcomes. Ongoing research directions and potential future developments are also outlined to provide readers with a foundation for further learning and clinical application.