Internet of Things (IoT) is a pervasive technology covering many applications areas (Smart Mobility, Smart Industry, Smart Healthcare, Smart Building, etc.). Its success and the technology evolution allow targeting more complex and critical applications such as the management of critical infrastructures and cooperative service robotics, which requires real time operation and a higher level of intelligence in the monitoring-control command for decision-making. Furthermore, these applications type need to be fully validated in advance considering that bugs discovered during real operation could cause significant damages. In order to avoid these drawbacks, IoT developers and system integrators need advanced tools and methodologies. This paper presents a methodology and a set of tools, defined and developed in the context of the BRAIN-IoT European Union (EU) project. The overall framework includes both Open semantic models to enforce interoperable operations and exchange of data and control features; and Model-based development tools to implement Digital Twin solutions to facilitate the prototyping and integration of interoperable and reliable IoT system solutions. After describing the solution developed, this paper also presents concrete use cases based on the two critical systems mentioned above, leveraging the application scenarios used to validate the concepts developed and results obtained by the BRAIN-IoT project.