The manufacturing world is experiencing what many recognize as “the fourth industrial revolution”, characterized by production lines turning into complex cyber-physical systems (CPSs). This transformation offers unprecedented opportunities but brings a series of intellectual and engineering challenges. The DeFacto (Design Automation for Smart Factories) project aims at advancing the field of CPS design and its automation by developing novel modeling paradigms, scalable algorithms, and tools to aid the design of smart manufacturing systems, ultimately fostering their widespread adoption.