Description:The impact of crop protection products on pollinating insects, particularly honeybees, is a critical consideration for ecological safety. Beyond acute toxicity, sublethal effects can potentially disrupt honeybee behavior, compromising pollination efficiency. Traditional assessment methods, reliant on visual observations, may not be optimal for capturing sublethal effects. In this study, we delved into molecular mechanisms underlying sublethal effects, employing three distinct platforms: whole-tissue transcriptomics, spatial transcriptomics, and metabolomics. Our findings reveal valuable insights into honeybee toxicity, with certain approaches demonstrating superiority in elucidating tissue-specific and treatment-specific responses, especially untargeted metabolomics tend to be a valuable tool for new bee-friendly agrochemical development. This research will aid in screening new molecules for pollinator safety and contribute to developing strategies that enhance crop yield while maintaining ecological sustainability.