Background: FoundationOne CDx (F1CDx) is a US FDA-approved companion diagnostic test to identify patients who may benefit from treatment in accordance with the approved therapeutic product labeling for 28 drug therapies. Tumor profiling with F1CDx detects genomic findings with evidence of additional clinical significance. This study analyzes the breadth and impact of clinical decision insights from F1CDx clinical reports across solid tumors. Methods: F1CDx consecutive reports (n = 109,695) were retrospectively analyzed for the type and frequency of clinically significant predictive, prognostic, and diagnostic genomic alterations and signatures in common cancer types and across solid tumors. Predictive markers were defined as therapeutically relevant markers in drug labels or NCCN guidelines or targets of ESCAT evidence Tier I/II (Mateo et al., 2018; PMID: 30137196). Prognostic and diagnostic markers were determined in accordance with NCCN, ESMO, or WHO guidelines. We also describe the frequency and targets of interventional clinical trials with targeted therapies or immune checkpoint inhibitors that were matched to tumor profiles based on clinical or strong preclinical evidence. Results: Predictive genomic findings of clinical significance were identified in more than half of non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer (BC), and melanoma (MEL) tissue samples; over a third of ovarian cancer (OC), urothelial carcinoma (UC), and head and neck squamous cell carcinoma (HNSCC); approximately a fourth of prostate cancer (PC), gastro-esophageal adenocarcinoma (GEA), cholangiocarcinoma (CA), and glioma (GL) samples; and one in 18 pancreatic adenocarcinoma (PA) samples (Table). Prognostic markers were reported for patients with NSCLC (18%), CRC (10%), BC (16%), PC (25%), CA (8.1%), MEL (24%), GL (74%), or HNSCC (7.1%). Diagnostic markers were frequently detected for patients with GL and noted for patients with BC, GEA, or MEL (Table). Interventional clinical trials were evidence-matched to most F1CDx tumor profiles (89%, range 82% in PC to 99% in PA), with the targets of approved therapies accounting for a small subset of targets in clinical development. Conclusions: F1CDx reports support clinical decision making by interpreting predictive, prognostic, and diagnostic markers according to professional guidelines as well as investigational markers for the enrollment in clinical trials.