Upper tract urothelial carcinoma is a rare disease. Due to its late presentation, a significant number of patients are diagnosed with an advanced or metastatic tumor stage. There are still unmet needs in the preoperative assessment, due to suboptimal current staging tools. The challenge lies in the balance between over- and undertreatment. Risk stratification strategies can help refine treatment for each individual patient. Radical nephroureterectomy with bladder cuff excision is the standard treatment for advanced non-metastatic disease. A template-based lymph node dissection can help improve prognosis and staging to guide decision making regarding adjuvant chemotherapy. Recent evidence indeed supports the use of perioperative systemic chemotherapy. While recent level one evidence supports the use of adjuvant platinum-based chemotherapy, the evidence for the use of neoadjuvant chemotherapy is still being collected. Cisplatin-based chemotherapy remains the standard of care for metastatic or unresectable UTUC in cisplatin-fit patients. Checkpoint inhibitors they have been approved in the first-line treatment of cisplatin ineligible PDL-1-positive tumors and in second line in patients who failed platinum-based chemotherapy. As UTUC has a luminal-papillary T-cell depleted contexture and high FGFR3 expression, FGFR3-targeting agents promise to become a successful therapeutic option.