While traditional 2D cell monocultures have been the cornerstone of safety assessments, they fall short in replicating the intricate biological processes within the human body. By leveraging cutting-edge in vitro technologies, advanced 3D cell models offer a more accurate and predictive framework for assessing the potential health impacts of (nano)materials and exploring new directions for (nano)carriers in a medical context. These projects pioneers developing sophisticated 3D culture systems that mimic the body’s key physiological barriers—the lung, intestine, and skin—that are reliable, relevant, and predictive.