Cellular therapeutics are poised to be a next pillar of medicine along with small molecules and biologics. These living drugs have a unique capacity for more complex decision-making and therapeutic responses, potentially alleviating the need for chronic treatment. Next-generation cell therapies will need to adapt and respond to disease progression, essentially functioning as microscopic “physicians” capable of sensing, diagnosing, and eradicating disease via multifaceted mechanisms that are difficult to resist yet similar to our natural immune system. Advances in engineered T cell therapeutics are being FDA approved and are now transforming treatment plans for cancers that previously had few therapeutic options. While there have been unprecedented complete responses in a subset of hematological malignancies, the current therapies can show significant toxicity and on the other hand show a lack of efficacy in solid tumors. Beyond cancer, engineered cell therapies could have significant impact in the treatment of autoimmunity, metabolic disorders and in regenerative medicine. This conference will therefore cover next-generation cellular engineering approaches designed to tackle refractory diseases such as solid tumors, while also addressing the higher safety requirements for diseases beyond late-stage metastatic cancers. This conference brings together clinically minded cell therapists, synthetic biologists, genome and protein engineers, systems biologists, and immunologists; this combined expertise is essential to establish cells as a safe and effective therapeutic strategy across a range of diseases. Smart cellular therapeutics of the future must be easily customizable, have intrinsic control systems to prevent toxicity, and be able to overcome rapidly evolving mechanisms preventing disease resolution; this conference aims to address these topics by convening global experts across a range of relevant disciplines.