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The effectiveness of cancer treatment strongly depends on the early detection of the disease. Currently, the most common diagnostic method, tissue biopsy, takes time and can be damaging to the patient. Circulating cancer biomarkers such as circulating tumor DNA, micro-RNA (miRNA), tumor proteins, exosomes, and circulating tumor cells have repeatedly demonstrated their viability as targets for minimally invasive cancer detection through liquid biopsies. However, among other things, achieving a great sensitivity of detection is still challenging due to the very low concentration of biomarkers in fluid samples. This review will discuss how the recent advances in nanoparticle-based biosensors are overcoming these practical difficulties. This report will be focusing mainly on optical transduction mechanisms of metal nanoparticles (M-NPs), quantum dots (QDs), and upconversion nanoparticles (UCNPs).