AbstractCancer remains one of the most complex and challenging diseases in mankind. To address the need for a personalized treatment approach for particularly complex tumor cases, molecular tumor boards (MTBs) have been initiated. MTBs are interdisciplinary teams that perform in‐depth molecular diagnostics to cooperatively and interdisciplinarily advise on the best therapeutic strategy. Current molecular diagnostics are routinely performed on the transcriptomic and genomic levels, aiming to identify tumor‐driving mutations. However, these approaches can only partially capture the actual phenotype and the molecular key players of tumor growth and progression. Thus, direct investigation of the expressed proteins and activated signaling pathways provide valuable complementary information on the tumor‐driving molecular characteristics of the tissue. Technological advancements in mass spectrometry‐based proteomics enable the robust, rapid, and sensitive detection of thousands of proteins in minimal sample amounts, paving the way for clinical proteomics and the probing of oncogenic signaling activity. Therefore, proteomics is currently being integrated into molecular diagnostics within MTBs and holds promising potential in aiding tumor classification and identifying personalized treatment strategies. This review introduces MTBs and describes current clinical proteomics, its potential in precision oncology, and highlights the benefits of multi‐omic data integration.