The design and synthesis of high-nuclear polyoxometalates (POMs) utilizing secondary building blocks (SBB) is attractive and challenging. Herein, four new high-nuclear polyoxovanadates (POVs), {V20S2In42P12 (CO2) } (1), {V20Mo2In4P12 (C2O4) 2} (2), {V12P6SPb2} (3) and {V12P6SCd2} (4), were successfully synthesized under solvothermal conditions by incorporating transition metals into POVs. All the structures are constructed from the tetragonal {V5 (PhPO3) 4} SBB, wherein five {VO5} square pyramids are interconnected by edge-sharing modes, and four phenylphosphonic acid ligands further coordinate with vanadium cations. Compounds 1 and 2 have similar structures in which two {V10 (PhPO3) 6 (SO4) In2} or {V10 (PhPO3) 6 (MoO4) In2} clusters are bridged by formate or oxalate ligands. While compounds 3 and 4 are constructed from {V12 (PhPO3) 6 (SO4) } cluster doped with transition metals Pb or Cd. Notably, compound 4 demonstrated efficient catalytic activity for sulfide oxidation.