Recently, many saturated bioisosteres of benzene ring have been developed, and their application in drug development has been evaluated. Most of these are caged hydrocarbons, which have rigid skeletons and three-dimensional spaces. Recent efforts to synthesize these caged hydrocarbons have enabled access to multi-functionalized congeners that are expected to be (bio)isosteres of multi-functionalized benzenes. This review article summarizes recently reported methods to obtain multi-functionalized (typically more than disubstituted) caged hydrocarbons.