he mechanisms controlling the nanostructuring of thin metal-on-oxide films by nanosecond pulsed excimer lasers are investigated. When permitted by the interfacial energetics, the breakup of the metal film into nanoscale islands is observed. A range of metals (Au, Ag, Mo, Ni, Ti, and Zn) with differing physical and thermodynamic properties, and differing tendencies for oxide formation, are investigated. The nature of the interfacial metal-substrate interaction, the thermal conductivity of the substrate, and the initial thickness of the metal film are all shown to be of importance when discussing the mechanism for nanoscale island formation under high fluence irradiation. It is postulated that the resulting nanoparticle size distribution is influenced by the surface roughness of the initial film and the Rayleigh instability criterion. The results obtained are compared with simulations of the heat transfer through the film in order to further elucidate the mechanisms. The results are expected to be applicable to the laser induced melting of a large range of different materials, where poor wetting of substrate by the liquid phase is observed.