There is an increasing interest in using three-dimensional (3D) cell-based assays for modeling tumors, organs, and other tissues. Significant progress has been made in formation of such structures to recapitulate the in vivo environment but performing complex assays with them can be challenging. The Pu·MA System is designed to automate a wide variety of 3D cell-based assays used for toxicity testing and oncology discovery as well as diabetes and metabolic disease research. At its core is a microfluidic flowchip that has specially designed chambers to protect sensitive cell structures and automatically perform media exchanges, compound additions, supernatant sampling, or other assays steps. The system fits into standard incubators and provides gas exchange to the cell sample chambers to keep cells happy. Complex assay protocols can be setup to automatically run from hours to days. It also can run low-volume immunoassays and is ideal for applications where samples are limited such as small animal studies. The system fits seamlessly into your current laboratory workflow using standard pipettes and assay reagents. We will describe several applications of the Pu·MA System using spheroids for oncology drug discovery and metabolomic profiling.