<p>Selective oxidation of aromatic alkanes is a key reaction to produce high-value chemicals in the chemical industry. However, the strong C–H bonds and inert chemical properties of aromatic alkanes render the oxidation process difficult, thereby making the development of promising and sustainable catalysts highly desirable. Herein, a resin-assisted coordination co-assembly strategy is developed to synthesize heterometal-doped mesoporous Co₃O₄ with abundant oxygen vacancies, enabling precise control over both composition and pore structure. The site-specific Mn doping at octahedral sites of mesoporous Co₃O₄ promotes the formation of oxygen vacancy with enhanced activity. Density functional theory calculations further demonstrate that Mn doping in mesoporous Co₃O₄ reduces the oxygen vacancy formation energy, induces the electronic structure modifications and introduces the defect energy levels, finally promoting the efficient catalytic oxidation of a series of aromatic alkanes. Representatively, Mn-doped mesoporous Co₃O₄ exhibits remarkably outstanding catalytic activity, achieving 37% conversion of ethylbenzene and 97% selectivity for acetophenone under solvent-free conditions.</p>