Over a decade ago, collaborating academic cancer centers formed the Oncology Research Information Exchange Network® (ORIEN) to develop a patient-driven, federated infrastructure for oncology research. Aster Insights is the network's operational, commercial, and research partner. Together ORIEN and Aster Insights have built a unique multimodal dataset on the active engagement and consent of patients who opted into the Total Cancer Care® (TCC) protocol to contribute their data and biospecimens for research. Over 400,000 cancer patients have been enrolled in TCC, >32,500 of which have an in silico "Avatar" generated to represent their individual patient experience and molecular profile to support a broad range of network and industry research use cases. We provide an overview of ORIEN's evolution, demonstrate the power of our data resources through a landmark analysis of >37,000 tumors across all cancer types collected for the Avatar program, and provide a vision for ORIEN to fuel collaborative research.