Abstract: Disclosed herein include systems, methods, compositions, and kits for the combined analysis of circulating cell-free nucleic acids and single cells in peripheral blood. The method can comprise isolating cell-free nucleic acids (cfNA), immune cells, leukocytes, and/or circulating tumor cells (CTCs) from a biological sample derived from a subject (e.g., a blood sample). The method can comprise performing high-throughput single cell sequencing assays. The method can comprise generating values for one or more genomic properties, one or more expression properties, and/or one or more variant properties based on sequence reads generated from said sequencing assays. Cancer prediction scores, MRD scores, and/or therapeutic efficacy scores can be generated based on the values of said properties. The methods provided herein can yield improved sensitivity and specificity in non-invasive blood-based oncology diagnostics.