Clinical trial data reveals that combining enfortumab vedotin with pembrolizumab before and after bladder cancer surgery significantly improved pathological complete response rates compared to standard chemotherapy. The antibody-drug conjugate paired with PD-1 blockade delivered measurable tumor shrinkage in the perioperative window. This represents a meaningful shift toward precision immunotherapy in urothelial carcinoma, where traditional platinum-based regimens have dominated for decades. The dual-agent approach leverages complementary mechanisms—targeted drug delivery via nectin-4 binding and checkpoint inhibition—potentially overcoming resistance patterns seen with single-agent treatments. For patients facing radical cystectomy, this combination could reduce surgical complexity and improve long-term outcomes. However, the perioperative timing requires careful toxicity monitoring, as both agents carry distinct side effect profiles that may complicate surgical recovery. The approach builds on growing evidence that immunotherapy works best when the immune system can respond to tumor antigens released during treatment, making the pre-surgical window particularly strategic. While promising, broader adoption will depend on longer-term survival data and careful patient selection criteria.