An improved understanding of the interactions of transition-metal (TM) nanoparticles with Lewis acids/bases will facilitate the design of more efficient catalysts. Therefore, Pt-14, Pt-13, Pt-12, and Ni-12 nanoparticles have been studied at the TPSSh/Def2-TZVP level of density functional theory (DFT). Surface electrostatic potential [V-S(r)] maps are used to analyze the Lewis acidic and basic properties of all nanoparticles and indicate that the interactions of Pt and Ni nanoparticles are governed by sigma(d)-holes and sigma(s) -holes, respectively. Lewis acids (Na+, HF) and a Lewis base (H2O) have been tested as ligands to probe the local interaction proficiencies. The comparison between binding energies and V-S(r) shows that the lowest minimum (V-S,V-min) and highest maximum (V-S,V-max) of V-S(r) on each particle can predict the most favorable binding site for the Lewis acids and base, respectively. V(S,min )can also rank the different binding strengths of Na+ and HF with the nanoparticles. For H2O, the binding strength versus V-S,V-max correlation is better for Ni-12 than for the Pt nanoparticles. This observation is discussed in relation to charge transfer/polarization and structural deformation upon interaction. In light of our findings, we compare the catalytic potential of Ni to the less abundant but more commonly used Pt.