Global (phospho)proteome profiling of patient tumor tissue adds a new angle to the ongoing precision oncology trials INFORM and MASTER that stratify patients based on genomic, epigenomic and transcriptomic signatures for individualized molecular treatment recommendations. To add the functionally and therapeutically important layer of the (phospho)proteome, we developed a robust workflow to generate comprehensive (phospho)proteome profiles within a two-week turnaround time from sample arrival to MTB discussion. A newly developed approach to infer aberrant activity of druggable signaling pathways using expression data of >8,000 proteins and 20,000 phosphosites per patient in a cohort of 300 sarcoma patients covering more that 35 sarcoma subtypes allows us to add critical information towards improved mapping of a tumor’s molecular biology. First results indicate that the additional (phospho)proteomic layer has great potential to refine stratification of individual patients. The project is still active and extends beyond the funding period.