Gene expression is the fundamental driving force that coordinates normal cellular processes and adapts to dysfunctional conditions such as oncogenic development and progression. While transcription is the basal process of gene expression, RNA transcripts are both the templates that encode proteins as well as perform functions that directly regulate diverse cellular processes. All levels of gene expression require coordination to optimize available resources, but how global gene expression drives cancers or responds to disrupting oncogenic mutations is not understood. Post-transcriptional coordination is controlled by RNA regulons that are governed by RNA-binding proteins (RBPs) and noncoding RNAs (ncRNAs) that bind and regulate multiple overlapping groups of functionally related RNAs. RNA regulons have been demonstrated to affect many biological functions and diseases, and many examples are known to regulate protein production in cancer and immune cells. In this review, we discuss RNA regulons demonstrated to coordinate global post-transcriptional mechanisms in carcinogenesis and inflammation.