Complex biological environments and multiple physiological barriers significantly impede efficient accumulation and penetration of nanomaterials within tumor tissue for therapy. In situ energy conversion of nanomotors features autonomous movements and improves cancer treatment. However, one of the key challenges is to prepare nanomotors with an adequately small size, good biocompatibility, and precise positioning. Herein, we demonstrate a simple, ultrasmall, versatile, and real-time motion guidance strategy for magnetocatalytic CoPt@graphene navigators (MCGNs) that can enable highly efficient propulsion in the presence of H2O2 or magnetic actuation. MCGNs act as highly diffusive delivery vehicles to promote tumor tissue targeting, and the amount of drug in the tumor was three times than without navigation. By engaging movements powered through in situ energy conversion, MCGNs gain considerable propulsion to penetrate a cell’s membrane and enhance intracellular delivery.