Presentations at ESMO highlighted two actionable developments: circulating tumor DNA (ctDNA) assays are demonstrating utility in guiding adjuvant therapy decisions and reducing overtreatment in bladder and colon cancer trials, and tumor microenvironment (TME) profiling is spawning first‑in‑human programs. Investigators reported ctDNA‑guided de‑escalation strategies with promising early outcomes and safety, while translational studies linking TME niches to response produced multiple FIH launches. The data underscores growing clinical adoption of molecular monitoring and TME‑targeted approaches.