The ability to detect and quantify more types of biomolecules at higher resolutions is crucial for our understanding of biological functions in cells and tissues. For example, single-cell level analyses by fluorescence-based flow cytometry have been a mainstay of immunologic inquiry for nearly four decades. Flow cytometry, which can provide data on ploidy, immuno-phenotype, frequency of cell subsets, expression levels of proteins, and function in single cells, has revolutionized our understanding of cellular individuality in immune function. Our laboratory uses two recently developed technologies, mass cytometry and multiplexed ion beam imaging (MIBI), which facilitate high dimensional (up to 50 parameters), quantitative analysis of molecules at single-cell resolution to enable a deeper understanding of how the immune system interacts with cancer cells. Better understand the underlying mechanism of the dysregulations of immune cells within tumor microenvironment could potentially lead to the design of therapeutic strategies to enhance or reinvigorate the anti-tumor effector functions.