Mixed self-assembly of ligands 1 and 2, PXDA (3), and Pd(NO3)2 afforded metal organic polyhedra (MOP 1 - MOP 3) which bear 24 covalently attached CB[7] and cyclooctyne moieties. Post assembly modification (PAM) of MOP 3 by covalent strain promoted alkyne azide click reaction provided MOP 4 R bearing covalently attached functionality (PEG, sulfonate, biotin, c-RGD, fluorescein and cyanine). Orthogonal CB[7] guest mediated non-covalent PAM of MOP 4 R with Ad-FITC afforded MOP 5 RGD Ad-FITC and MOP 5 biotin 0020Ad-FITC. Flow cytometry analysis of the uptake of MOP 5 RGD Ad-FITC toward U87 cells demonstrated improved uptake relative to control MOP lacking c-RGD ligands. These results suggest a broad applicability of orthogonally functionalizable (covalent and non-covalent) MOPs in targeted drug delivery and imaging applications.