High-entropy intermetallic (HEI) nanomaterials have recently been established as a representative class of high-performance nanocatalysts. However, the synthesis of HEI nanomaterials remains a significant challenge, with only a limited number of types being reported to date. This review aims to provide a systematical overview of the current state of research on HEI nanomaterials. The synthesis strategies are first discussed, with a special emphasis on the pivotal role that supports play in the formation of HEI nanomaterials. Following this, we provide a summary of key catalytic applications and focus on the structure–performance relationships. Finally, the review concludes by discussing the challenges faced in this area and suggesting potential research directions for the future.