Metal‐organic frameworks (MOFs) are a promising class of materials for catalysis, offering unique opportunities for designing efficient and selective catalysts. In this study, we have focused on the synthesis and catalytic activity of a novel mixed metal MOF, Ce/Zr−UiO‐66@LiOtBu, designed for the rapid hydrolysis of chemical warfare agents simulants: dimethyl 4‐nitrophenyl phosphate (DMNP) and 2‐chloroethyl ethyl sulfide (CEES). This MOF was thoroughly characterized using powder X‐ray diffraction (PXRD), BET surface area, and inductively coupled plasma optical emission spectrometry (ICP‐OES). The catalytic performance of Ce/Zr−UiO‐66@LiOtBu was monitored in the hydrolysis of DMNP and CEES by using 31P NMR and GC‐MS respectively. Remarkably, the MOF demonstrated rapid and efficient catalytic activity, breaking the P−O bond in DMNP with 2 min and the hydrolysis of CEES was observed in less than 45 min The results suggest the potential application of Ce/Zr−UiO‐66@LiOtBu as a robust catalyst in the detoxification of chemical warfare agent simulants. Our findings highlight the novelty of Ce/Zr−UiO‐66@LiOtBu as a catalytically active MOF, showcasing the successful integration of cerium ions and lithium tert‐butoxide to enhance basicity.