The post-genomic era promises to pave the way to a personalized understanding of disease processes, with technological and analytical advances helping to solve some of the world's health challenges. Despite extraordinary progress in our understanding of cancer pathogenesis, the disease remains one of the world's major medical problems. New therapies and diagnostic procedures to guide their clinical application are urgently required. OncoTrack, a consortium between industry and academia, supported by the Innovative Medicines Initiative, signifies a new era in personalized medicine, which synthesizes current technological advances in omics techniques, systems biology approaches, and mathematical modeling. A truly personalized molecular imprint of the tumor micro-environment and subsequent diagnostic and therapeutic insight is gained, with the ultimate goal of matching the “right” patient to the “right” drug and identifying predictive biomarkers for clinical application. This comprehensive mapping of the colon cancer molecular landscape in tandem with crucial, clinical functional annotation for systems biology analysis provides unprecedented insight and predictive power for colon cancer management. Overall, we show that major biotechnological developments in tandem with changes in clinical thinking have laid the foundations for the OncoTrack approach and the future clinical application of a truly personalized approach to colon cancer theranostics.