Simultaneously adjusting the coordination environment of Fenton-like catalysts and engineering their architectures is a viable strategy to promote catalytic reaction. Herein, two-dimensional (2D) porous core-shell FeSe_2+x @C nanocube superlattices (NCSLs) with unsaturated selenium are for the first time prepared via one-step selenization of Fe₃O₄@C NCSLs and tested for peroxymonosulfate (PMS)-based Fenton-like reaction. The 2D porous superlattice structure can preferably expand Fe sites exposure and accelerate the large-scale transport and utilization of nanocrystals. The unsaturated selenium can optimize the electronic state of cationic Fe, not only promoting the Fe³⁺/Fe²⁺ cycle, regulating PMS adsorption, and improving the charge density, but also accelerating interfacial electron transport of the catalyst to lower the energy barrier of PMS decomposition to yield SO₄^•−. This work demonstrates a new application of nanocrystal superlattices and provides more insights to active components of catalyst design for enhancing catalytic activity via structural control and coordination engineering in various application scenarios.