The inclusion of intracellular protein detection enables the measurement of pivotal proteins in cancer mechanisms, including apoptosis (BCL2 family proteins), transcription factors (GATA3), tumor suppressors (TP53), as well as phosphorylated proteins involved in cell growth signaling pathways (phosphorylated ERK, STAT3 proteins). This is the first-ever method that provides a solution to effectively link surface and intracellular protein measurement with targeted DNA analysis. With this approach, single-cell readout of genotypic and phenotypic information can be collected together, allowing concurrent analyses of cancer clonal evolution and driver protein expression.