We exploit the nanoparticle biomolecule corona formation in order to facilitate the comprehensive proteomic analysis of complex biological fluids. We employ nanoparticles as scavenging agents to uncover blood-buried molecular fingerprints of low abundance, otherwise “masked” under the overwhelming signal of highly abundant proteins (such as albumin and immunoglobulins). Our work has demonstrated that analysis of the biomolecule corona fingerprinting by mass spectrometry overcomes the critical ‘signal-to-noise’ hurdle and facilitates an in depth analysis of the blood circulation proteome. Our ultimate goal is to develop a nanoparticle-enabled integrative multi-omics blood analysis workflow.