The European Union’s goal to reduce pesticide risk, exemplified by restrictions on insecticides like neonicotinoids, necessitates a shift from single-substance risk assessment to a holistic evaluation of pest control strategies. To address this, a novel decision-support grid was developed that integrates 13 environmental, biodiversity, and human health risk indicators for multiple active substances across an entire crop season into a single Final Scenario Score (FSS), ranging from 0 to 1 (where 1 is the risk of the reference scenario). This framework was applied to three case studies in Belgium—sugar beet, apple, and pear cultivation—where neonicotinoid-based reference scenarios were compared with chemical and/or organic alternatives under low (best-case) and high (worst-case) pest pressure conditions. The results highlight the complexity of finding viable alternatives, with an FSS below 0.75 as the justification threshold. In sugar beet, only the best-case chemical alternative (FSS = 0.71) met the threshold, while worst-case chemical alternatives failed due to increased risk. For apple and pear, organic alternatives consistently showed low-risk scores (FSS 0.27–0.61) but faced important efficacy gaps against key insect. Chemical alternatives in orchards were justifiable in low-pressure scenarios (FSS 0.64–0.73) but failed under high pest pressure (FSS 0.91–0.93). This novel decision-support grid proves to be a valuable tool for guiding sustainable pest control strategies for regulators and field advisors.

The potential withdrawal of glyphosate necessitates a comprehensive evaluation of alternative weed control strategies that balances human health safety with environmental concerns. This study applied a decision-support grid to compare the impacts of glyphosate-based reference strategies against chemical and non-chemical alternatives across four Belgian case studies: pome fruit orchards, grassland renewal, arable weed patches, and railways. The assessment integrated twelve risk indicators including human, environmental and biodiversity risk, and life cycle assessment for global warming potential (GWP) into a Final Scenario Score (FSS). The results indicated that only one alternative strategy, the chemical alternative in local weed patch control, achieved the FSS threshold (<0.75) required to justify substitution (FSS = 0.70). Chemical alternatives in other case studies frequently shifted burdens; for instance, bio-herbicides in railways increased risks to residents and aquatic organisms compared to the reference. Conversely, mechanical and thermal alternatives eliminated chemical toxicity but resulted in GWP increases up to 32 times higher than glyphosate-based practices. These findings demonstrate that chemical substitutes often maintain toxicity risks while non-chemical strategies trade them for increased climate impacts. Consequently, a ban on glyphosate is currently unsupported by the environmental performance of available alternatives in these temperate high-intensity systems. Sustainable progress requires a transition period where optimized conventional strategies remain available within integrated weed management, while innovations in electrification and precision technology are accelerated to resolve current trade-offs.