The future of drug discovery and development lies in 3D human tissue models. The latest generation of 3D in vitro models are highly predictive, stable over long periods of time (thus appropriate for assessing complex treatment regimens), and permit the cultivation of organotypic tissues, composed of all the relevant cell types required to recapitulate human in vivo physiology. Enabling 3D cell-based technologies, such as microtissue plates and organ-on-a-chip systems as well as accessible endpoints have evolved rapidly and are ready for large-scale implementation in drug discovery and development workflows. In this tutorial, we will present our scalable 3D microtissues models composed of human primary cells for applications in metabolic disease discovery (liver disease/NAFLD/NASH, islet research/T1D/T2D), oncology (PDX and I-O), and safety assessment (liver toxicology). We also discuss specifically engineered, SBSS-compatible plates such as 96-well, 384-well and organ-on-a-chip formats, all highly compatible with state-of-the-art imaging and automation equipment as well as most assay endpoints. Our unique technology platform enables researchers to complement and reduce reliance on animal experiments, saving significant time and resources in the drug development process and ensuring higher confidence in decision making for later clinical stages.