The OncoIncytes™ platform enables high-purity capture and release of live single circulating tumor cells (sCTCs) without leukocyte contamination, allowing integrated DNA, RNA, and protein profiling from the same cell. In a study of 2,062 patients across 25 cancer types, sCTCs were detected in 83% of cases and nearly all metastatic samples, with feasibility also shown in cerebrospinal and pleural fluids. Importantly, 20–25% of ctDNA-negative patients harbored pathogenic sCTC mutations, and tri-omic analysis confirmed actionable concordance across DNA, RNA, and protein. In HER2+ breast cancer, sCTCs revealed copy number gains, RNA expression, and protein abundance—directly supporting ADC and bispecific development. This “cell biopsy” approach uncovers predictive biomarkers missed by ctDNA or tissue, accelerating drug development and patient stratification.