Acid-catalyzed skeletal C-C bond isomerizations are important benchmark reactions for the petrochemical industries. Among those, o-xylene isomerization/disproportionation is a probe reaction for strong Bronsted acid catalysis, and it is also sensitive to the local acid site density and pore topology. Here, we report on the use of phosphotungstic acid (PTA) encapsulated within NU-1000, a Zr-based metal organic framework (MOF), as a catalyst for o-xylene isomerization at 523 K. Extended X-ray absorption fine structure (EXAFS), P-31 NMR, N-2 physisorption, and Xray diffraction (XRD) show that the catalyst is structurally stable with time-on-stream and that WO clusters are necessary for detectable rates, consistent with conventional catalysts for the reaction. PTA and framework stability under these aggressive conditions requires maximal loading of PTA within the NU 1000 framework; materials with lower PTA loading lost structural integrity under the reaction conditions. Initial reaction rates over the NU-1000-supported catalyst were comparable to a control WQ(x)-ZrO2, but the NU-1000 composite material was unusually active toward the transmethylation pathway that requires two adjacent active sites in a confined pore, as created when PTA is confined in NU-1000. This work shows the promise of metal-oganic framework topologies in giving access to unique reactivity, even for aggressive reactions such as hydrocarbon isomerization.