Introduction: Cytokines are a diverse group of peptides produced by different cell types including cancer cells and various subpopulations of immune system cells. They exert their effects as cellular secreted mediators after binding to appropriate membrane receptors. Area covered: In this modern era of a multiomic approach to immuno-oncology this paper discusses the multiple roles of cytokines in oncology and our current understanding of the complex interactions between a tumor and host (in the so-called tumor microenvironment). Because of their pivotal role in biomedicine, we focus on critical comments about advantage between many techniques which are helping our understanding of the signal transduction process, gene activation, gene regulation and their clinical significance. Expert opinion: Integrated investigations based on a multiomic approach to the interactions between cells of the immune system and cancer, which focus at different cellular, molecular and nuclear levels, and involving proteomics, genomics, transcriptomics, metabolomics and pharmacogenomics, are expected to lead to improved cancer diagnoses and treatment in the future.