<p>Fe-based Metal–Organic Frameworks (MOFs) show promise as heterogeneous Fenton-like catalysts; however, in the removal of hydrophobic VOCs, traditional wet Fenton systems suffer from slow Fe³⁺/Fe²⁺ cycling and high gas–liquid mass transfer resistance, severely limiting their industrial application. To address these challenges, this study proposes a dual optimization strategy. Specifically, a gas-phase H₂O₂ Fenton-like system was constructed to overcome mass transfer limits, and multivalent Mn was introduced into the MIL-100(Fe) to accelerate the Fe²⁺/Fe³⁺ cycle. Among the synthesized catalysts, MIL-100(Fe₄Mn₁) (4FM) exhibited superior catalytic performance, achieving 85% toluene degradation efficiency and a capacity of 87.17&#xa0;μg C₇H₈/(g·min)) under optimized conditions, significantly outperforming its monometallic counterparts. Characterization results reveal that 4FM retains an ordered crystalline structure with highly dispersed active sites and an optimized pore architecture. Mechanistic studies indicate that Fe–Mn synergy induces an “electron pump” effect, utilizing the thermodynamic potential differences to accelerate the reduction of Fe³⁺ to Fe²⁺. Concurrently, the system establishes dual reaction centers (Fe and Mn), where efficient Mn²⁺/Mn³⁺/Mn⁴⁺ and Fe²⁺/Fe³⁺ redox cycles facilitate sustained gaseous H₂O₂ activation into hydroxyl radicals (·OH), promoting efficient toluene degradation. This study provides a promising strategy utilizing gas-phase Fenton-like catalytic technology to overcome kinetic and mass transfer bottlenecks in degrading of hydrophobic VOCs.</p> Graphical Abstract <p></p>