Open interoperability delivers on the promise of enabling vendors and developers to interact and interoperate, without interfering with anyone’s ability to compete by delivering a superior product and experience. In the absence of global IoT standards, the INTER-IoT voluntary approach will support and make it easy for any IoT stakeholder to design open IoT devices, smart objects, services, and complex systems and get them to be operative and interconnected quickly, thus creating new IoT interoperable ecosystems by using a bottom-up approach. In particular, INTER-IoT is based on hardware/software tools (INTER-Layer) granting multi-layer interoperability among IoT system layers (i.e. device, networking, middleware, application service, data and semantics), on frameworks for open IoT application and system programming and deployment (INTER-FW), and on a full-fledged CASE tool-supported engineering methodology for IoT systems integration (INTER-Meth). The INTER-IoT approach is notably exemplified through two use cases: INTER-LogP, involving interoperability of port logistics ecosystems, and INTER-Health, encompassing integration between e-Health at home and in mobility infrastructures.