A Nature Medicine real‑world analysis of 888 patients demonstrated that routine paired tumor‑normal whole‑genome sequencing (WGS) succeeded in 89% of cases with a median 6‑working‑day turnaround and identified potentially actionable biomarkers in 73% of patients. Biomarker‑informed treatment led 40% of patients to start targeted therapies within a year and was associated with a 31% longer median overall survival in the cohort. Practical note: WGS provides a tumor‑agnostic route to detect a broad spectrum of DNA‑based biomarkers in a single test, reducing tissue demands and speeding clinical decision‑making compared with sequential single‑marker assays.