The tumor microenvironment (TME) is a heterogeneous and continuously evolving system. Besides malignant cells, it is composed of numerous immune cells, astrocytes and other stromal cells, blood vessels, and extracellular matrix. Interactions of tumor with other cells produce an immunosuppressive milieu, thus impeding antitumor immunity. The advancements of single-cell techniques provide powerful means to scrutinize the tumor and TME at high resolution, shedding light on the pathogenic mechanisms and dysfunctions of antitumor immunity. Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) enables simultaneously single-cell RNA sequencing (scRNAseq) and the acquisition of both quantitative and qualitative information about surface proteins using oligonucleotide-tagged antibodies. By combining proteomic and transcriptomic data from the same single cell, CITE-seq has become one of the leading approaches for phenotyping discrete cell populations. The method has been successfully used to detect over a hundred epitopes per cell, adding an additional layer of information that, when integrated with transcriptomic data, enables the identification of cellular states and functions, as well as the prediction of cell trajectories, maturity, and interactions with other cells.