Energetic polyatomic cluster beams are increasingly used in materials processing and surface analysis applications. In secondary ion mass spectrometry (SIMS) such beams have previously been utilised to investigate the chemical distribution of organic molecules (polymers, biological molecules and pharmaceuticals etc). One important application is in organic electronics, where the depth-distribution of organic components is important in the device performance. Massive gas cluster ion beams (GCIBs) have produced more successful depth-profiles for organic electronic devices that smaller projectiles including SF5+ and C60+. However, further work is needed to investigate and optimise experimental parameters to deliver the necessary SIMS performance. This study focused on molecular depth profiling of organic insulator (PMMA) and semiconductor (PTAA and TIPS-pentacene) materials, in single and bi-layered combinations, utilising cluster SIMS, using C60+ and Arn+, at different temperatures and energies. In general, at room temperature, the best depth resolution was obtained, using large Ar-GCIBs of low energy per atom (E/n ~10 eV), in comparison with the smaller Ar-GCIBs or with C60+ beams at the same total impact energy. On materials which sputtering under C60+ bombardment, ion and neutral yields were greatest due to the higher E/n, compared with GCIBs. Data from PMMA show that the sputter yield under C60 and Arn projectiles conform to the published âuniversalâ dependence of Y/n to E/n. Depth profiling of the semiconductor compounds were unsuccessful, using C60+ projectiles. For depth profiles using large GCIB projectiles, an increase in the secondary ion yield was observed at the interface with the silicon substrate â a phenomenon which was not observed for the smaller projectiles. In general, the most successful depth profiles (i.e. more constant molecular and fragment secondary ion yields, observed at pseudo-steady-state regions) and best depth resolutions were obtained at cryogenic temperatures - conditions under which corresponding sputtering yields and secondary ion yields were suppressed.