Immunotherapies are coming to the forefront as a treatment paradigm in cancer with multiple US FDA approvals in recent years and a better understanding of their therapeutic mode of action. The control of tumor growth by the immune system is orchestrated by a complex array of cellular interactions and molecular pathways, both in the immune cells as well as the tumor. Although research over the past three decades has elucidated many aspects of tumor immunosurveillance, given the inherent complexity of the immune cell phenotypes and function, high-throughput molecular profiling ('omics') approaches have now become essential to support the discovery and development of new therapies. Technologies, such as DNA and protein microarrays, deep sequencing, mass spectrometry, as well as the computational methods for their analyses, are advancing the contributions of systems biology towards the development and mechanistic understanding of cancer immunotherapies. In this review, the authors illustrate this through some recently reported studies.