Schematic overview of Physiome-on-a-chip approach. The Physiome-on-a-Chip comprises bioengineered devices that nurture many interconnected 3D MPSs representing specified functional behaviors of each organ of interest, designed to capture essential features of in vivo physiology based on quantitative systems models tailored for individual applications such as drug fate or disease modeling. By interconnecting MPSs, dynamic multi-organ signaling can be recreated naturally through cytokine and hormone circulation, cell trafficking, and metabolic byproducts. Multi-MPS systems bridge the complexity gap between traditional in-vitro cell culture, animal models, and human patient samples, potentially providing better prediction of human responses at lower financial and ethical costs as compared to current methods of drug development. Illustration by Victor O. Leshyk.