The notion that the immune system is capable of recognizing and destroying cancer has become a clinical reality with the development, approval, and implementation of novel immunotherapies. Blockade of immune inhibitory receptors, adoptive T cell therapy, vaccination against tumor antigens, and engagement of innate immune pathways have all reached the standard-of-care arena. However, as many patients fail to respond to these therapies, there is much work to be done to bridge the gap and expand the circle of efficacy. Fundamental immunology research is identifying additional molecular and cellular features of regulation of endogenous anti-tumor immune responses. New approaches to T cell engineering are being investigated, and engineering of other immune cells is being pursued. Bioinformatic approaches to streamline neoantigen identification are being utilized, and novel vaccine platforms are being tested. Since a major determinant of efficacy is driven by the biology of the tumor microenvironment, single cell technologies and in situ tissue imaging are being carried out. Interrogation of patient samples is providing a key resource for understanding treatment failure, and molecular details of the tumor, genetics of the host, and the composition of the gut microbiome are features defined already that impact on immunotherapy outcomes. Analysis of each of these dimensions is pointing towards new therapeutic interventions.