<p>Catalyst design is often reaction-specific due to the lack of universal descriptors linking molecular structures to optimal active-site configurations. Here, we uncover a reactant-dependent volcano relationship in Pt-catalyzed dehydrogenation, governed by the Pt-Pt coordination number (CN_Pt-Pt). Using a tunable Pt/MgAl₂O₄ system, we identify optimal CN_Pt-Pt values of ~2.5, ~4.7, and ~7.0 for cyclohexane, methylcyclohexane, and decalin, respectively. This activity trend is explained by an orbital hybridization-guided mechanism, where optimal activity emerges from a balance between C-H bond activation and product desorption, mediated by the interactions between Pt d-orbitals and the π* orbitals of dehydrogenated intermediates. We introduce the LUMO energy of aromatic products as a universal electronic descriptor that serves as a proxy for π* orbital energy. LUMO energy shows strong linear correlations with the d-band center of Pt at the optimal CN_Pt-Pt, enabling rational tuning of electronic interactions across diverse reactants. The optimized Pt/MgAl₂O₄ catalyst delivers 2-3 times higher activity with &gt;100 h stability under industrial conditions at only 300 ^oC, offering a robust strategy for hydrogen release and active-site engineering in dehydrogenation catalysis.</p>