Analyzing circulating extracellular vesicles (EVs) or exosome promises to improve cancer diagnostics and enable serial patient monitoring during therapy. Establishing clinical EV tests, however, faces practical challenges: complex and lengthy sample workup; limited throughput and sensitivity of conventional assays; high equipment or test costs; and lack of clinically validated markers. In this presentation, we report key advances toward clinical EV analyses: i) development of a high-throughput assay strategy, HiMEX (high-throughput magneto-electrochemical exosome), and ii) assessment of EVs as a biomarker of colorectal cancer (CRC). HiMEX integrates magnetic capture with electrochemical detection within a single platform; we enrich cancer-specific EVs directly from plasma samples and profile their protein expression. This approach renders the assay fast (<1 hour) and scalable; we implemented a compact assay system for parallel detection (96-well format). Applying HiMEX, we profiled circulating EVs in clinical samples EVs were found to carry key protein signatures of tumor tissues, and by using a combination of markers, we achieved high diagnostic accuracies (>95%). Preoperative EV tests further showed this method’s prognostic potential for categorizing patients into high- and low-risk groups for 5-year disease-free survival. These outcomes demonstrate HiMEX’s clinical utility for timely, informed cancer care.