The exploration of nanoscale high-entropy intermetallic compounds (HEICs) represents a transformative frontier in materials science, particularly in catalysis. The unique combination of multi-element composition, long-range atomic ordering, and nanoscale dimensions endows HEICs with superior electronic, structural, and catalytic properties that surpass those of traditional metal catalysts. However, achieving both uniform multi-element mixing and long-range ordered structures at the nanoscale is challenging. Building on this, this review highlights the key role of configurational entropy, mixing enthalpy, elemental composition, and size effects in the stable formation of nanoscale HEICs through thermodynamic and kinetic analysis. The latest advancements and existing challenges in the design, synthesis, structure, and applications of HEIC catalysts are discussed, with a focus on exploring their synthesis–structure–performance relationships from multiple perspectives. We hope that this review will offer valuable insights for further exploration and development of HEICs in catalytic applications.