We are witnessing a renaissance in our understanding of the deep mechanistic interconnectedness of cardiovascular and metabolic disease, marked by a shift from siloed views of individual organs to an appreciation of dynamic interorgan communication. Exciting new science and technologies are beginning to elucidate how these complex diseases emerge from coordinated dysfunction across cardiac, metabolic, renal, skeletal muscle, hepatic, immune, and nervous systems. The therapies of tomorrow will rely on our ability to decipher this intricate crosstalk. This 3.5-day Keystone Symposium, Cardiometabolism and Interorgan Crosstalk: Novel Mechanisms and Therapies, convenes a diverse, multidisciplinary, and international community from academia, the private sector, and public institutions to explore groundbreaking insights and novel therapeutic strategies. Sessions will span immune and neurological mechanisms, human genetics, AI-driven target discovery and patient segmentation, muscle-liver-heart-renal axes, obesity’s systemic effects, and emerging therapies. Invited speakers will present their latest unpublished findings, with special emphasis on translation of these insights into clinical innovation. In addition to the scientific sessions, the program will feature dynamic workshops and career-building events, such as mentorship roundtables and interactive discussions with leaders from diverse professional backgrounds. By fostering deep scientific engagement across attendees from a broad array of fields, this meeting will provide a unique environment for catalyzing cross-disciplinary collaboration, which is essential for our collective ability to tackle the alarming societal burden of cardiometabolic disease. In partnership with the Endocrine Society, this symposium aims to inspire “bench-to-bedside-and-back” discoveries that hold the promise of reshaping prevention, diagnosis, and treatment for patients worldwide.