Nanoparticles of materials with layered structure are able to spontaneously form closed-cage nanostructures such as nested fullerene-like nanoparticles and nanotubes. This propensity has been demonstrated in a large number of compounds such as WS2, NiCl2, and others. Layered metal oxides possess a higher ionic character and consequently are stiffer and cannot be evenly folded. Vanadium pentoxide (V2O5), a layered metal oxide, has received much attention due to its attractive qualities in numerous applications such as catalysis and electronic and optical devices and as an electrode material for lithium rechargeable batteries. The synthesis by pulsed laser ablation (PLA) of V2O5 hollow nanoparticles, which are closely (nearly) associated with inorganic "fullerene-like" (NIF-V2O5) nanoparticles, but not quite as perfect, is reported in the present work. The relation between the PLA conditions and the NIF-V2O5 morphology is elucidated. A new mechanism leading to hollow nanostructure via crystallization of lower density amorphous nanoparticles is proposed. Transmission electron microscopy (TEM) is used extensively in conjunction with structural modeling of the NIF-V2O5 in order to study the complex 3-D structure of the NIF-V2O5 nanoparticles. This structure was shown to be composed of facets with their low-energy surfaces pointing outward and seamed by defective domains. These understandings are used to formulate a formation mechanism and may improve the function of V2O5 in its many uses through additional morphological control. Furthermore, this study outlines which properties are required from layered compounds to fold into perfectly closed-cage IF nanoparticles.