Abstract: To reveal the differences in the regulation of inclusions in Inconel 718 nickel-based superalloy by VIM-ESR and VIM-VAR secondary refining processes, consumable electrodes were prepared from the same heat of VIM master alloy, and comparative experiments were carried out under typical industrial process parameters. By combining ASPEX automated scanning electron microscopy, SEM-EDS inclusion characterization, thermodynamic calculations, and crystallographic misfit calculations, the types, number, size distribution, and radial evolution of inclusions in ingots produced by the two processes were systematically studied. The results show that inclusions in both ingots exhibit a radial gradient distribution, with the number of inclusions increasing from the core to the edge; however, the dominant inclusion types differ significantly. The ESR ingot is dominated by TiN inclusions and NbS-TiN composite inclusions, whereas NbS-TiN composite inclusions are overwhelmingly dominant in the VAR ingot. Within the parameter range of this study, the ESR ingot has a higher total inclusion count but exhibits significantly better removal capability for harmful large inclusions >10 μm than the VAR ingot; the VAR ingot has a lower total inclusion count but retains more large inclusions. The difference in solidification kinetics caused by the radial cooling-rate gradient is the key cause of the inclusion distribution: the high cooling rate at the edge leads to solute supersaturation and triggers burst nucleation of fine TiN/NbS-TiN; slow cooling in the core provides sufficient diffusion and ripening, promoting the growth of large inclusions. The ESR molten pool is shallower and the local solidification rate is higher; meanwhile, the slag removes some oxide inclusions that act as heterogeneous nucleation cores, resulting in abundant fine TiN inclusions. The solidification conditions of VAR promote the segregation of Nb and S, inducing heterogeneous nucleation of NbS on pre-existing TiN and causing the enrichment of NbS-TiN composite inclusions at the edge. The two-dimensional lattice misfit between TiN and NbS is about 9.37%, which is higher than the ideal threshold for heterogeneous nucleation. The formation of NbS-TiN composite inclusions is jointly controlled by solute segregation, interfacial energy, and crystallographic conditions. In engineering applications, process performance cannot be judged solely by the total inclusion content; process selection should be comprehensively conducted according to the component’s sensitivity to inclusion size and type. For extreme cleanliness requirements, triple melting or multi-parameter synergistic optimization can be adopted to simultaneously reduce the total inclusion content and achieve deep removal of large inclusions.