Safe-and-sustainable-by-design (SSbD) is central in the European Chemicals Strategy for Sustainability, yet a common understanding of what SSbD is in concept and in practice is still needed. A comparison of current SSbD descriptions and approaches was made and lessons learned were derived from value chain discussions (packaging, textile, construction, automotive, energy materials, electronics, and fragrances value chains) to help provide input on how to implement SSbD in practice. Five important building blocks were identified: design, data, risk and sustainability governance, competencies, and social and corporate strategic needs. Other lessons learned include the identification of the biggest safety and sustainability challenges in a lifecycle-thinking approach towards the development of purpose-driven innovations, and connecting trans-disciplinary experts to the innovation process, already from the early phases. A clear understanding of what SSbD is and how to implement the SSbD framework is needed with clear procedures and incentives to support the industrial sector, especially SMEs.