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In the title compound, {[NiTb2(C14H8N2O5)4(H2O)4]·4H2O}n, the TbIII ion is coordinated by one water molecule and seven O atoms from four 5-(pyridine-4-carboxamido)isophthalate (L) ligands in a distorted square-antiprismatic arrangement, while the NiII ion, lying on an inversion center, is six-coordinated in an octahedral geometry by two pyridine N atoms, two carboxylate O atoms and two water molecules. One L ligand bridges two TbIII ions and one NiII ion through two carboxylate groups and one pyridine N atom. The other L ligand bridges two TbIII ions and one NiII ion through two carboxylate groups, while the uncoordinating pyridine N atom is hydrogen bonded to an adjacent coordinating water molecule. Extensive O—H...O, N—H...O and O—H...N hydrogen bonds play an important role in stabilizing the crystal structure.