DNA sequencing has identified recurrent mutations that drive the aggressiveness of prostate cancers. Surprisingly, the influence of genomic, epigenomic, and transcriptomic dysregulation on the tumor proteome remains poorly understood. We profiled the genomes, epigenomes, transcriptomes, and proteomes of 76 localized, intermediate-risk prostate cancers. We discovered that the genomic subtypes of prostate cancer converge on five proteomic subtypes, with distinct clinical trajectories. ETS fusions, the most common alteration in prostate tumors, affect different genes and pathways in the proteome and transcriptome. Globally, mRNA abundance changes explain only ∼10% of protein abundance variability. As a result, prognostic biomarkers combining genomic or epigenomic features with proteomic ones significantly outperform biomarkers comprised of a single data type. Display omitted •A comprehensive proteomic analyses of localized prostate cancers•Integration of all levels of the central dogma (DNA → RNA → protein)•ETS fusions have divergent effects on transcriptome and proteome•Combining genomics and proteomics improves biomarker performance Sinha et al. determine the proteogenomic landscape of localized, intermediate-risk prostate cancers and show that the presence of ETS gene fusions has one of the strongest effects on the proteome. Prognostic biomarkers that integrate multi-omics significantly outperform those comprised of a single data type.