ASSIST-IoT aims at design, implementation and validation of an open, decentralized reference architecture, associated enablers, services and tools, to assist human-centric applications in multiple verticals. Instances of the architecture will be supported by key enablers, like edge/fog computing, (semi-)autonomy, distributed AI, smart devices, interoperability, Distributed Ledger Technology (DLT) atop a smart network infrastructure, with low latency capabilities, allowing execution of context-aware applications with new interaction interfaces (e.g. AR/VR/MR), etc. The proposed solution will integrate AI-based functions transferring intelligence closer to the edge (data sources), including devices. The reference architecture, and developed enablers, will be validated in three realistic pilots: (i) port automation; (ii) smart safety of workers, and (iii) cohesive vehicle monitoring and diagnostics. The proposed approach is focused on the edge-fog-cloud continuum model.