Soft-tissue sarcomas (STS) with complex karyotypes constitute a puzzling and extremely diverse group of mesenchymal aggressive tumors, that can occur as early as childhood and in almost any part of the body, have unknown etiology, and poor response to standard treatments. Carcinosarcomas are a rare entity within all epithelial tumors with epithelial and mesenchymal (sarcoma-like) features, thought to originate through metaplastic transformation of the epithelial component. SARCOMICS aims to prove the molecular relatedness between different types of STS with complex karyotypes and between STS and carcinosarcomas. It also aims to understand their progression through the identification of the evolutionary trajectories and cellular processes leading to high-grade undifferentiated tumors. These findings are to unveil common therapeutic vulnerabilities. To fulfil these objectives, SARCOMICS will take advantage of a unique biorepository containing more than 50,000 biological specimens, including multi-regional and temporal samples, on which state-of-the-art technologies including single-cell sequencing, spatial profiling, and long-read sequencing will be applied. Patient-derived tumor organoid models will also be generated to validate the proposed transformation and convergence processes. SARCOMICS will address a major knowledge gap in the field of STS and carcinosarcomas and will open new avenues to improve the clinical management and prognosis of these neglected diseases. Beyond generating capacity building and know-how for cancer genomics studies in general, and the obvious interest for the sarcoma field, SARCOMICS has also the potential to transform our approach for studying and classifying rare cancers and rare subtypes of common cancers by capitalizing on their similarities to discover their common weaknesses.