A real‑world study of paired tumor‑normal whole‑genome sequencing (WGS) in 888 solid‑tumor patients demonstrated high technical success (89%), a median six‑day turnaround, and identified potentially actionable DNA biomarkers in 73% of cases. The Nature Medicine report linked biomarker‑informed therapy to longer median overall survival (+31%). WGS flagged reimbursed and experimental treatment options and solved or guided therapy in many cancers of unknown primary. Clinically relevant germline variants were discovered in 6.5% of patients, and 40% of patients started biomarker‑guided therapy within one year. The data support routine WGS as a comprehensive molecular diagnostic to inform precision oncology and illustrate operational feasibility in a comprehensive cancer center setting.