Immunotherapeutic strategies are well established for the treatment of autoimmune diseases and in transplantation medicine since many years; only recently significant improvements in cancer therapy were achieved with the introduction of therapeutic antibodies along with conventional chemotherapy. A paradigm shift for the immunotherapeutic treatment of cancer began with the introduction of checkpoint inhibitors illustrating the potency of immunotherapeutic strategies by releasing a broad productive anti-tumor and eventually autoimmune response. The most promising, albeit also the most sophisticated and challenging approach of interventional immunology, is the targeted redirection of immune cells by genetic engineering as individually tailored “living drugs”, as illustrated by the success of chimeric antigen receptor (CAR)-modified T cells for the treatment of leukemia and lymphoma. Emerging synthetic immunology approaches provide a broad set of novel tools for immune cell (re-)programming to equip effector cells with defined, specific and enhanced anti-tumor capacities, probably also for solid tumors. Being dedicated to this fascinating field of research the Regensburg Center for Interventional Immunology (RCI) hosted the “Synthetic Immunology and Environment-adapted Redirection of T cells” symposium in the Thon-Dittmer-Palais Regensburg on 17–18 July, 2019. The aim of the symposium was to discuss convergent mechanisms of immune regulation and T cell reprogramming in cancer and autoimmunity, to identify and dissect programs in immune cells that determine their tissue function and to define which capacities immune cells need to cure diseased tissues. With this goal about 150 scientists discussed over two days the recent developments in synthetic biology approaches and genetic engineering of immune cells ranging from sensor systems towards effector functions for the development of environment-smart immune cell therapies to treat cancer and autoimmune disorders.