ENABLE-S3 is an industry-driven EU-project, aspiring to substitute today’s cost-intensive validation and verification efforts by virtual and semi-virtual testing and verification, coverage-oriented test selection methods and standardization to pave the way for efficient development of highly automated and autonomous systems (ACPS). Driven by 13 industrial highly automated systems use-cases from 6 industry sectors (automotive, aerospace, rail, maritime, health, farming), the ENABLE-S3 consortium develops an European cross-domain framework for cost-efficient verification and validation of the functionality, safety and security of ACPS. ENABLE-S3 is use-case driven, representing relevant environments and scenarios. Each of the models, methods and tools integrated into the validation platform can be applied to at least one use case (under the guidance of the V&V methodology), where they are validated and their usability demonstrated.