Mass spectrometry lipidomics dataset analyzing degradation pathways of ionizable lipids in mRNA lipid nanoparticles (LNPs) exposed to environmental stressors. UHPLC–TIMS-TOF MS was used to characterize lipid oxidation products and structural degradation of DLin-MC3-DMA (MC3), SM-102, and ALC-0315 under UV irradiation, oxidative conditions, thermal exposure, and freeze–thaw cycling.