Experiments have shown that the use of polyatomic projectiles in secondary ion mass spectrometry (SIMS) increases the secondary yield of molecular ions by an order of magnitude or more. This observation, coupled with the availability of an SF5 + source, has sparked renewed interest in SIMS measurements for characterizing a wide range of molecules. In this paper, we present the results of molecular dynamics simulations with Xe and SF5 projectiles that show that the molecular ion yield from bombarded organic surfaces is enhanced by the use of polyatomic projectiles. The model systems consist of a monolayer of twenty biphenyl molecules on two different substrates, Cu(001) and Si(100), and are designed as a prototype for experimentally studied systems. Our results show that the structure of the lattice is the critical factor. The breakup of the SF5 cluster within the more open lattice of the Si(100) substrate initiates collision cascades that lead to substrate atoms hitting the biphenyl molecules from below, which results in a greater yield of ejected molecules. The results are important because they predict that the nature of the substrate or matrix is a critical factor in maximizing the molecular ion yield.