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Circulating tumor DNA (ctDNA) has emerged as a dynamic biomarker for MRD detection. It enables real\u2010time disease monitoring, prognostication, and often therapeutic decision\u2010making. Two major ctDNA approaches exist, tumor\u2010informed and tumor\u2010agnostic, and they differ in sensitivity, specificity, and clinical feasibility. Recent clinical trials have supported a prognostic and predictive utility of ctDNA MRD in gastrointestinal, lung, breast, and other malignancies, with positive postoperative or post\u2010treatment MRD status correlating with higher recurrence risk and inferior survival outcomes. However, integration into clinical practice remains limited by challenges, including tumor heterogeneity, variable ctDNA shedding across tumor stage, location and timing, lack of standardized assay interpretation, and cost\u2010effectiveness concerns. Emerging technologies such as methylation\u2010based sequencing, ultra\u2010deep next\u2010generation sequencing, and machine learning\u2013driven risk models hold promise for improving detection accuracy and clinical applicability. Ongoing clinical trials are expected to determine the impact of earlier MRD detection and intervention on patient outcomes, potentially supporting the broader adoption of ctDNA MRD. 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