The regulation of the morphology and the composition of Pt-based materials is a promising strategy to improve their catalytic performance for the methanol oxidation reaction (MOR). In this work, we report the preparation of multinary PtPdNiP truncated octahedral mesoporous nanocages (PtPdNiP TOMNs) with a well-defined structure. Benefitting from their porous outer surface, hollow structure, and compositional effect, the as-obtained PtPdNiP TOMNs exhibit excellent catalytic activity and durability in the MOR. This work would provide a promising route for the rational design and development of metal–nonmetal nanomaterials with an improved performance in fuel cells and other applications.