Abstract A persistent challenge in utilizing gold nanostructures for surface‐enhanced Raman scattering (SERS) lies in positioning analytes into the nanoscale hotspots that maximize SERS performance and achieve universal substrates. Here, a novel mesoporous nano‐pockets strategy is proposed to design high performance universal SERS substrates by precisely capturing target molecules into plasmonic hotspots. This is achieved through utilizing mesoporous silica as nano‐pockets for confined growth of short Au thorns on the Fe 3 O 4 core (Fe 3 O 4 @sAT@mSiO 2 ), whilst the vertically open nano‐pockets structure with nanospace large enough at tips of short Au thorns to capture target molecules through hydroxyl group on the mesoporous surface. The electromagnetic field enhancement obtained from the Au thorns with an average gap size of 3 nm is sufficient to amplify the Raman signal peaks of the trapped molecules. Therefore, the as‐prepared Fe 3 O 4 @sAT@mSiO 2 proves to be ultrasensitive and reliable SERS detection of 15 kinds of drugs, with all limits of detection lower than those reported in the current literature. Moreover, the experimental findings are further corroborated by simulations using the molecular dynamics and finite element method. These mesoporous‐confined Au thorn nano‐pockets with accessible hotspots promote future use for developing the universal SERS method in various fields.