The withdrawal of the most harmful pesticides from the EU market is necessary to mitigate major environmental harm, but is leaving many farmers in a desperate position. CROP-SAFE has identified 3 critical cases of food crops under threat from rapidly spreading pests, whilst go-to pesticides are identified by ECHA as candidates for imminent withdrawal, i.e. Candidates for Substitution (CfS) and Substances of Very High Concern (SVHC). 1. Potato crops, widely threatened by Potato cyst nematode (PCN). The approval period for the leading active against PCN, Fosthiazate (CfS), expires in 2027. 2. Tomato crops, suffering from losses up to 65% due to Root knot nematode (RKN). The approval period for Metham sodium (CfS, SVHV), one of the most widely uses actives against RKN, expires in 2025. 3. Banana crops, suffering from the European emergence of Banana Weevils (BW). Growers are using Lambda-cyhalothrin (CfS, SVHC) to manage BW, but the approval period lapses in 2026. CROP-SAFE will develop a holistic package of tools (bioactives, delivery materials, formulations and decision support models) for effective and sustainable management of PCN, RKN, and BW in these crops. Using scalable supplies of bio-based residues (aquatic biomass, forestry residues, spent coffee grounds and fungal waste) and three biorefining partners, CROP-SAFE will down-select the most effective boiactives and delivery materials as a basis for new, SSbD crop protection products. Field trials will be supported by decision support models, overcoming challenges associated with the variable performance of bioactives in different environmental conditions. The CROP-SAFE consortium combines the expertise of 3 Universities (UA, CNR, IQS-URL) and 4 RTOs (CPI, VITO, LEITAT, JHI) with material processing capacity in 3 biorefineries (BOR, ABA, KB) a leading developer of precision agriculture solutions, SE, and a cooperative, COPLACA, representing 3,200 farmers.