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Abstract This work explores the possibility of depth profiling of inorganic materials with Megaelectron Volt Secondary Ion Mass Spectrometry using low energy primary ions (LE MeV SIMS), specifically 555 keV Cu2+, while etching the surface with 1 keV Ar+ ions. This is demonstrated on a dual-layer sample consisting of 50 nm Cr layer deposited on 150 nm In2O5Sn (ITO) glass. These materials proved to have sufficient secondary ion yield in previous studies using copper ions with energies of several hundred keV. LE MeV SIMS and keV SIMS depth profiles of Cr-ITO dual-layer are compared and corroborated by atomic force microscopy (AFM) and time-of-flight elastic recoil detection analysis (TOF-ERDA). The results show the potential of LE MeV SIMS depth profiling of inorganic multilayer systems in accelerator facilities equipped with MeV SIMS setup and a fairly simple sputtering source.