Recurrence following colorectal cancer(CRC)surgery poses a major challenge to long-term patient survival. Early and accurate prediction of recurrence is essential for formulating individualized adjuvant treatment strategies. Circulating tumor DNA (ctDNA) and systemic inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), serve as two important types of biomarkers, providing prognostic information from the perspectives of tumor molecular residual disease and host immune-inflammatory responses, respectively. However, the application of either marker alone has certain limitations. This article focuses on exploring the biological synergistic mechanisms and clinical predictive value of their combined application. ctDNA can directly reflect minimal residual disease, with its warning window typically occurring several months earlier than radiographic recurrence. Systemic inflammatory markers, on the other hand, reflect the state of the tumor-associated immune microenvironment. The two are closely related in the pathophysiological process of "inflammation promoting the release and persistence of ctDNA". Currently, although prospective evidence on their combined use is still accumulating, theoretical models and preliminary studies in other cancer types suggest that combined detection may enable more refined stratification of recurrence risk, thereby guiding individualized clinical decisions, including intensified adjuvant therapy and anti-inflammatory interventions. At present, this combined strategy still faces challenges such as high detection costs, insufficient standardization, and complexity in result interpretation. In the future, rigorous prospective cohort studies should be conducted, integrating multi-omics data and artificial intelligence analysis to construct and validate multimodal prediction models that incorporate ctDNA and inflammatory markers, thereby advancing the precision management of postoperative recurrence in CRC.