Human T cells are a highly heterogeneous population and can recognize a wide variety of antigens by their T cell receptors (TCRs). Tumor cells display a large repertoire of antigens that serve as potential targets for recognition, thus making T cells in the tumor micro-environment more complicated. Making a connection between TCRs and the transcriptional information of individual T cells will be interesting for investigating clonal expansion within T cell populations under pathologic conditions. Advances in single cell RNA-sequencing (scRNA-seq) have allowed for comprehensive analysis of T cells. In this review, we briefly describe the research progress on tumor micro-environment T cells using single cell RNA sequencing, and then discuss how scRNA-seq can be used to resolve immune system heterogeneity in health and disease. Finally, we point out future directions in this field and potential for immunotherapy.