Triclosan　(TCS),　an　antimicrobial　compound,　is　knownto　have　potentialendocrine-disruptive　properties,　but　the　underlying　toxic　mechanismsat　the　metabolic　level　are　not　well　understood.　Here,　we　applied　metabolomicsand　lipidomics　combined　with　mass　spectrometry　imaging　(MSI)　to　unveilthe　mechanisms　of　the　enhanced　growth　of　MCF-7　breast　cancer　cellspheroids　(CCS)　exposed　to　TCS.　To　obtain　a　wide　coverage　of　metabolitesand　lipids　by　using　MSI,　we　used　techniques　of　matrix-assisted　laserdesorption/ionization　(MALDI)　and　MALDI　coupled　with　laser-postionization.The　results　showed　that　TCS　and　TCS　sulfate　penetrated　into　the　entirearea　at　0-3　h　and　both　localized　in　the　inner　area　at　6　h.After　24　h,　a　portion　of　two　compounds　was　released　from　CCS.　Omicdata　indicated　that　TCS　exposure　induced　alterations　via　several　pathways,including　energy　metabolism　and　biosynthesis　of　glycerophospholipidsand　glycerolipids.　Further　MSI　data　revealed　that　the　enhancementof　energy　supply　in　the　peripheral　area　and　the　increase　of　energystorage　in　the　inner　area　might　contribute　to　the　enhanced　growthof　MCF-7　breast　CCS　exposed　to　TCS.　This　study　highlights　the　importanceof　integrating　metabolite　distributions　and　metabolic　profiles　toreveal　the　novel　mechanisms　of　TCS-triggered　endocrine　disruptingeffects.　Minimal　research　exists　onexploring　the　mechanisms　of　triclosan-inducedendocrine　disrupting　effects　at　metabolic　levels.　This　study　fillsthis　gap　by　using　a　triclosan-exposed　breast　cancer　cell　spheroidmodel.