Three novel 3D pillared-layer heterometallic lanthanide-transition-metal (hetero-Ln-TM) compounds, namely, Ln(2)Cu(7)I(6)(ina)(7)(H2O)(6) center dot H2O [ina = isonicotinic acid; Ln = Ce (1), Sm (2)] and Er-4(OH)(4)Cu5I4(ina)(6)(na)(2,5-pdc) center dot 0.3H(2)O (3; na = nicotinic acid, 2,5-pdc = 2,5-pyridinedicarboxylic acid), have been obtained by incorporating different metal clusters as building blocks under hydrothermal conditions. Compounds 1 and 2 are isostructural and consist of two distinct building units of dimeric [Ln(2)(ina)(6)] cores and inorganic 2D [Cu8I7](n)(n+) layers based on the [Cu3I3] and [Cu4I3](+) clusters. Compound 3 is constructed from decanuclear [Cu10I8](2+) clusters and inorganic 1D [Er-4(OH)(4)](n)(8n+) cluster chain-based layers, which represent the first example of a 3D hetero-Ln-TM constructed by the combination of two distinct types of metal cluster units of a 1D [Er-4(OH)(4)](n)(8n+) cluster polymer and a transition-metal cluster. It is interesting that decarboxylation occurred in the ortho position and 2,5-pdc(2-) was partially transformed into na(-) under hydrothermal conditions. Compounds 1 -3 represent good examples of using different metal cluster units to construct fascinating 3D hetero-Ln-TM frameworks.