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Circulating tumor cells (CTCs) represent a powerful, minimally invasive window into tumor biology and disease evolution. Technological progress over the past decade has markedly improved the ability to isolate, preserve, and interrogate viable CTCs, transforming them from simple prognostic markers to functional tools for precision oncology. Advances in microfluidic platforms, immunomagnetic enrichment, aptamer-based capture, and nanostructured interfaces have expanded the efficiency and fidelity of CTC recovery, enabling comprehensive molecular profiling and ex vivo analysis. These innovations have paved the way for the development of CTC-derived preclinical models, including xenografts, organoids, and chorioallantoic membrane assays, which recapitulate patient-specific tumor heterogeneity and support individualized drug-sensitivity testing. In this review, we summarize current technologies for CTC isolation, outline recent achievements in functional and pharmacological characterization, and discuss the translational impact of CTC-derived models. We further identify persistent challenges and emerging opportunities, highlighting how integration of multi-omics platforms, artificial intelligence, and standardized workflows may accelerate the clinical implementation of CTC-guided personalized therapy.