The European Chemicals Strategy for Sustainability introduces the Safe-and-Sustainable-by-Design (SSbD) concept. It goes beyond current regulatory compliance and aims to ensure the safety and sustainability of (novel) chemicals, materials, products, and processes. It starts at early-innovation stages and follows the chemicals and materials throughout their entire lifecycle. This perspective paper presents an SSbD roadmap that explores current needs and gives recommendations for the practical operationalization of SSbD in industrial operations and processes. This roadmap was co-created including different SSbD stakeholders and encompasses three interlinked agendas on (i) research needs, (ii) skills, competencies, and education needs, and (iii) knowledge and information sharing needs. An overarching need is the development of a common understanding of SSbD with clear definitions, terminology, and criteria. In addition, SSbD operationalisation needs to be pragmatic and applied as early as possible in the innovation process. From a research needs perspective, it is essential to integrate the different fields of innovation, safety, and sustainability. From a skills, competencies and education perspective, targeted training is needed that balances the depth and breadth of SSbD required for a specific audience. These trainings should not only convey hard/technical skills, but also soft/social skills to support more sustainability-oriented decisions on all levels. From a knowledge and information sharing perspective, a strategic plan and a trusted environment are needed to support dialogue between all SSbD stakeholders while at the same time protecting intellectual property (IP). The roadmap should help to coordinate planning for the implementation of SSbD at industrial, academic, policy, and regulatory level by defining actions and raise strategic efforts.