Safe-and-Sustainable-by-Design (SSbD) advanced materials and chemicals (AMCs) are a central requirement for reaching the ambitious goal of making Europe a digitally enabled circular, climate-neutral, and sustainable economy. Novel AMCs need to provide the high functionality required for their advanced applications, whilst simultaneously exhibiting improved safety and sustainability performance considering the complete value chain and life cycle, as outlined in the SSbD framework proposed by the EU Joint Research Centre [1], adopted in the Commission Recommendation of 8 Dec. 2022 [2], and supplemented by methodological guidance [3]. The Innovative Advanced Materials Initiative (IAM-I, www.iam-i.eu) has set out for four priority areas for intense research and innovation (R&I) on advanced materials, i.e. energy, mobility, construction, and electronics, and the health care sector will follow as next priority area. “PLANETS – Plasticizers, fLame-retardants, and surfactANts: new alternatives validating the safE-and-susTainable-by-deSign approach” is a HORIZON project facilitating the twin green and digital transition in global economy via replacing AMCs relevant to a wide range of advanced material innovation markets within the before-mentioned priority areas. This workshop session will cover the background of SSbD, exemplify the workflow of SSbD-guided innovation dissected into three different Tier levels based on state of knowledge and availability of data at different innovation stages, and overview opportunities and challenges when operationalizing SSbD on real-life cases. In conclusion, integrated and well-balanced workflows organized across the diverse dimensions of SSbD facilitate early-stage decision-making processes during innovation of AMCs, while SSbD approaches promote responsible R&I in industry and academia.