Sn-beta zeolites prepared using different recipes feature very different catalytic activities for aqueous phase glucose isomerization, suggesting the presence of different active sites. A systematic study of the morphology and atomic-level structure of the materials using DNP NMR spectroscopy in combination with first-principles calculations allows for the discrimination between potential sites and leads to a proposal of specific structural features that are important for high activity. The results indicate that the materials showing the highest activity possess a highly hydrophobic, defect-free zeolite framework. Those materials show so-called closed and associated partially hydrolyzed Sn(IV) sites in the T6 and T5/T7 lattice positions. On the other hand, postsynthetically synthesized Sn-beta samples prepared in two steps via dealumination and subsequent solid-state ion exchange from Al-beta show significantly lower activity, which is associated with a hydrophilic framework and/or a lower accessibility and different lattice position of the Sn sites in the zeolite crystal. Further, we provide a method to distinguish between different Sn sites on the basis of NMR cartography using chemical shift and chemical shift anisotropy as readily measurable parameters. This cartography allows identifying not only the nature of the active sites (closed, defect-open, and hydrolyzed-open) but also their position within the BEA framework.