Modern medicine has given rise to an array of treatment options for diseases, such as acute myeloid leukemia (AML). Cancer is a heterogeneous mixture of cells with varied states, and the best treatment options for an individual patient requires an understanding of the disease state at the cellular level. A single-cell multi-omics approach is the only way to achieve full resolution of the disease at the cellular level, revealing the interplay between genotype and phenotype. The Tapestri Platform enables comprehensive identification of cell subpopulations through single-cell multi-omics profiling. The platform discerned single nucleotide variants (SNVs), copy number variations (CNVs), and cell surface protein expression in single cells from a mixture of AML cell lines and an AML research sample. The results demonstrate that subpopulations are not consistently defined by one genetic or phenotypic factor alone, but by multiple parameters and are irretrievable by bulk sequencing methods. The multi-omics data generated by the Tapestri Platform is consistent with gold-standard techniques currently used for traditional omics analysis of AML samples.