MoS2 modification by doping transition metals is an effective way to change the Mo–S bond energy by taking advantage of the electronic variability of the d orbitals of transition metals. Herein, this study investigates the doping effect of different transition metals onto MoS2 edge sites through DFT calculations. To screen out the metal additive effect, different transition metals were doped to the MoS2 edge sites to see the effect on generating S vacancies that were generally regarded as the active sites. DFT simulation results proved that the ability of the valence electrons to populate the orbitals with the greatest overlap with the orientation of the edge Mo–S bond was a major factor in how simple it was to create S vacancies at the Mo-edge and S-edge sites. For the transition metals, the vacancy formation energy increases with the increase of periodic number for the same group, while decreases with the increase of the atomic weight for the same period. This implied that the upper right corner transition metals in the Periodic Table could be selected to modify MoS2 to obtain the minimum vacancy formation energy. Therefore, nickel and cobalt are the best choice as the doping element for modifying MoS2.