<p>A key challenge in cancer precision oncology is the limited ability of genomic analyses to accurately predict changes in protein expression or function, even though proteins serve as the main targets of numerous modern therapies. Bridging this gap necessitates precise quantification of proteins and their post-translational modifications (PTMs). Recent advances in mass spectrometry (MS)-based proteomics now enable large-scale, quantitative characterization of proteins and PTMs in tumor tissues. To link genomic aberrations to cancer phenotypes, the emerging field of proteogenomics integrates proteomic data, including PTMs, with genomic, epigenomic, and transcriptomic information. This comprehensive approach offers a deeper understanding of cancer biology at multiple levels. This review highlights recent advancements in MS-based proteomics, key discoveries in cancer proteogenomics, and the transformative potential of this field in decoding the complexities of cancer across diverse dimensions.</p>