Advances in immune profiling techniques have dramatically changed the cancer immunotherapy and monitoring landscape. High-throughput protein and gene expression technologies have paved the way for the discovery of therapeutic targets and biomarkers, and have made monitoring therapeutic response possible through the ability to independently assay the phenotype, specificity, exhaustion status, and lineage of single T cells. Although valuable insights into response profiling have been gained with current technologies, it has become evident that single-method profiling is insufficient to accurately capture an antitumor T cell response. We discuss and propose new methods that combine multiple axes of analysis to provide a comprehensive analysis of T cell repertoire in the fight against cancer.