We investigated the functionalization of pristine and post-deposition-annealed atomic layer deposition (ALD)-grown MoS₂ films on silicon wafers with the polyoxometalate (POM) (nBu₄N)₃[HV₁₂O₃₂Cl(DyPc)] (referred to as V₁₂-DyPc) and its impact on the optical and electronic properties of 2D semiconductor layers. Thin-film analysis confirms the formation of high-quality, polycrystalline MoS₂ after annealing. The deposition of V₁₂-DyPc induces a concentration-dependent reduction in A exciton emission and the emergence of negatively charged trion (A^–) photoluminescence (PL), evidencing systematic charge transfer. Studies on thinner MoS₂ layers grown by metal-organic chemical vapor deposition (MOCVD) corroborate this effect. Short-range surface ordering of POMs is detected on pristine, amorphous MoS₂. Notably, V₁₂-DyPc exhibits identical multilevel switching behavior on both amorphous and polycrystalline, annealed MoS₂. On MoS₂, V₁₂-DyPc shows a significantly reduced lateral electronic density distribution (3 nm compared to 7 nm on highly oriented pyrolytic graphite (HOPG)) and a more positive first reduction potential (3.1 V vs. 2.1 V, respectively). These changes are due to the substantially increased surface roughness of MoS₂ relative to the atomically flat HOPG substrate, and to the impact of a modified chemical environment on MoS₂. Density functional theory (DFT) and molecular mechanics simulations reveal face-on bonding geometries, altered redox energetics, and substrate-dependent shifts in electronic states.