Surface and interface designs are an efficient strategy to fabricate innovative and advanced catalysts. A prerequisite for this is a fundamental understanding of the structure-performance relations of catalyst nanoparticles, which, however, remains a formidable challenge due to the complexity of heterogeneous catalysis. Recent progresses in catalytic nanocrystals with uniform and well-defined structures, in situ characterization techniques, and theoretical calculations have offered opportunities for the fundamental studies of heterogeneous catalysis, and the achieved outputs are turning the innovation of efficient catalysts via surface and interface designs into a reality. Herein, the recent advances in the fundamental-understanding-directed rational surface and interface designs for heterogeneous catalysis, including crystal phase design, morphology/facet design, and size design, are presented. Perspectives are also discussed for the innovation of efficient catalysts via the fundamental-understanding-directed surface and interface designs followed by controlled synthesis.