In the era of immuno-oncology, circulating immune biomarkers provide insight into tumor–immune interactions. Blood-based immune profiling includes cellular, soluble, nucleic acid-based, and EV-associated markers. Circulating immune cells and cytokines can inform treatment response and prognosis. However, immune phenotypes are highly sensitive to pre-analytical conditions and physiological variability. Single time-point measurements often lack interpretive power compared to longitudinal monitoring. Integration with tumor-derived analytes such as ctDNA, CTCs, and EVs enhances biological context. Multi-dimensional immune profiling offers potential for predicting immunotherapy outcomes. This chapter discusses both the promise and limitations of circulating immune biomarkers. It positions immune markers as complementary components of liquid biopsy-based precision medicine.