Fe-active sites in Metal Organic Frameworks (MOFs) are emerging as promising candidates for selective oxidation of methane to methanol (MTM), mimicking the unique selectivity of Fe-enzymes. Herein, we propose a combined XAS/XRD investigation for targeting Fe(II) sites in three novel biomimetic MOFs, capable to form Fe(IV)=O species active towards MTM oxidation in mild conditions using O2 as oxidant and RT, making them a rare example for MTM by O2. Experimental evaluation of the catalytic path is critical to understand the reactivity, to this aim, we propose this in situ experiment targeting Fe(II) sites during MTM oxidation with the plus of performing the characterization of the elusive Fe(IV)=O intermediate, stable in these materials when kept at 150 K, making possible its detection with spectroscopic methods. The resulting electronic/structural insights on Fe active sites and reactive intermediates are expected to unlock unprecedented spectroscopic details and structural information.