The research on circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) has emerged in immune-oncology (IO) clinical studies, aiding in assessing drug efficacy, patient stratification, and treatment decision-making for solid tumors. Despite the absence of approved ctDNA-based companion diagnostic (CDx) assays for IO therapies, studies highlight the value of ctDNA monitoring for patient management in IO settings. With various ctDNA MRD tests launched, understanding tests have become immensely significant to clinical uses. The presentation will delve into the potential of ctDNA MRD in IO, technical approaches for detection, and real-world applications in clinical studies.