The concept of personalized medicine has predominantly been pursued through genomic and transcriptomic technologies, leading to the identification of multiple mutations in a large variety of cancers. However, it has proven challenging to distinguish driver and passenger mutations and to deal with tumor heterogeneity and resistant clonal populations. More generally, these heterogeneous mutation patterns do not in themselves predict the tumor phenotype. Analysis of the expressed proteins in a tumor and their modification states reveals if and how these mutations are translated to the functional level. It is already known that proteomic changes including posttranslational modifications are crucial drivers of oncogenesis, but proteomics technology has only recently become comparable in depth and accuracy to RNAseq. These advances also allow the rapid and highly sensitive analysis of formalin-fixed and paraffin-embedded biobank tissues, on both the proteome and phosphoproteome levels. In this perspective, we highlight pioneering mass spectrometry-based proteomic studies that pave the way towards clinical implementation. We argue that proteomics and phosphoproteomics could provide the missing link to make omics analysis actionable in the clinic. This article is protected by copyright. All rights reserved.