Catalytic site isolation in nanoreactors is a desirable feature because it permits complex transformations with more than one catalyzed step, each step needing a different catalyst, to be run in a single vessel. Various types of one-pot multiple step processes may be distinguished. The present chapter focuses on those where two or more steps are chemically incompatible by the nature of the catalysts and/or the reagents, but the process is rendered possible by compartmentalization of the mutually destructive components. A requirement to accomplish this goal is the absence of interpenetration between the compartments holding the incompatible functions. This can more easily be achieved by anchoring the different components on rigid scaffolds, but successful processes may also result when using non-miscible flexible scaffolds and even when using physically compatible nanogels that cannot interpenetrate because of a sufficiently dense cross-linking network. This chapter provides a short history of site isolation for catalytic or stoichiometric one-pot tandem process and then reviews the recently developed nanostructured materials able to promote non-orthogonal tandem catalytic processes.