Magnetic　nano-detection　systems　for　monitoring　symptoms　subsequent　to　cancer　treatment　have　drawn　significant　attention　within　the　domain　of　therapeutic　diagnostics.　However,　the　weak　affinity　of　target　analytes　with　traditional　magnetic　SERS　substrate　and　complex　matrix　interference　impede　the　achievement　of　high　sensitivity　and　precision　necessary　for　practical　H2O2　applications.　Herein,　Based　on　Fe3O4@SiO2@Au　seed-MBN　(4-mercaptobenzoonitrile)　@Au　(FSAMA)　substrate　and　the　electro-driven　adsorption　strategy,　this　study　develops　a　SERS　sensor　for　quantification　of　H2O2　residue.　The　magnetic　core　can　improve　cytocompatibility　and　reduce　cytotoxicity　with　the　inorganic　SiO2　layer.　Au@DTNB　(5,5＇-Dithiobis-(2-nitrobenzoic　acid))　@Ag　molecules　can　be　adsorbed　onto　the　＇hotspot＇　region　of　FSAMA　substrate　to　obtain　enhanced　SERS　signals.　Though　the　enhanced　second-harmonic　generation　(SHG)　effect,　the　H2O2　oxidizes　the　Ag　layer　of　FSAMA-Au@DTNB@Ag　to　Ag　(I),　which　will　significantly　cause　changes　in　the　SERS　signal,　which　is　improved　by　2-3　orders　of　magnitude.　The　incorporation　of　inner-layer　labeling　molecules　within　the　Au　NPs　enhances　the　stability　of　SERS　signal　output　while　maintaining　excellent　Raman　signal　contrast　for　H₂O₂　detection.　In　summary,　the　FSAMA-SERS　sensing　system　developed　for　detecting　H₂O₂　levels　may　serve　as　a　promising　platform　for　diagnostic　and　prognostic　monitoring,　applicable　across　a　wide　range　of　complex　serum　samples.　©　2025　Elsevier　B.V.