In this contribution, we describe a post-assembly modification approach to selectively coordinate transition metals in Pd₁₂L₂₄ cuboctahedra. The herein reported approach involves the preparation of Pd₁₂L₂₄ nanospheres with protonated nitrogen donor ligands that are covalently linked at the interior. The so obtained Pd₁₂(LH⁺)₂₄ nanospheres are shown to be suitable for coordinative post-modification after deprotection by deprotonation. Selective formation of tetra-coordinated M^B in Pd₁₂M^B₆L₂₄, tri-coordinated M^B in Pd₁₂M^B₈L₂₄ nanospheres and two-coordinated M^B in Pd₁₂M^B₁₂L₂₄ nanospheres is achieved as a result of different nitrogen donor ligands. A combination of pulsed EPR spectroscopy (DEER) to measure Cu–Cu distances in the different spheres, NMR studies and computational investigations, support the presence of the complexes at precise locations of the Pd₁₂M^B₆L₂₄ nanosphere. The general post-assembly modification methodology can be extended using other transition metal precursors or supramolecular systems and can guide precise formation and investigation of novel transition metal-complex containing nanospheres with well-defined composition.