Liquid biopsy, a minimally invasive alternative to tissue biopsy, has emerged as a promising diagnostic and prognostic tool. It involves screening disease-related markers from blood or other biofluids to achieve early diagnosis, timely prognosis, and effective treatment. However, the detection of biomarkers such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) remains challenging due to their low abundance and complexity. Optical biosensors based on nanomaterials offer enhanced sensitivity and practicality for liquid biopsy. This review highlights recent advancements in optical nanomaterials for the sensitive detection of various biomarkers, including proteins, peptides, ctDNA, microRNAs, exosomes, and CTCs. Each study tailors optical nanomaterials to improve sensing performance and meet the specific requirements of each biomarker. The unique optical properties of metallic nanoparticles, quantum dots, upconversion nanoparticles, silica nanoparticles, polymeric nanoparticles, and carbon nanomaterials are leveraged to develop efficient detection mechanisms. These advances in liquid biopsy using optical nanomaterials provide opportunities to overcome conceptual and practical challenges, offering a deeper understanding of biomarker characteristics and disease mechanisms.Liquid biopsy, a minimally invasive alternative to tissue biopsy, has emerged as a promising diagnostic and prognostic tool. It involves screening disease-related markers from blood or other biofluids to achieve early diagnosis, timely prognosis, and effective treatment. However, the detection of biomarkers such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) remains challenging due to their low abundance and complexity. Optical biosensors based on nanomaterials offer enhanced sensitivity and practicality for liquid biopsy. This review highlights recent advancements in optical nanomaterials for the sensitive detection of various biomarkers, including proteins, peptides, ctDNA, microRNAs, exosomes, and CTCs. Each study tailors optical nanomaterials to improve sensing performance and meet the specific requirements of each biomarker. The unique optical properties of metallic nanoparticles, quantum dots, upconversion nanoparticles, silica nanoparticles, polymeric nanoparticles, and carbon nanomaterials are leveraged to develop efficient detection mechanisms. These advances in liquid biopsy using optical nanomaterials provide opportunities to overcome conceptual and practical challenges, offering a deeper understanding of biomarker characteristics and disease mechanisms.