Using ab initio density functional theory (DFT), the adhesive behavior of NiAl(110)/Al2O3(0001) interface in thermal barrier coatings was systematically studied with an emphasis on the effects of alloying additives and impurity elements. To reveal possible atomic-scale mechanisms, the separations between certain atoms at the interface, the electron localization function (ELF), and the electron density of states (DOS) are thoroughly investigated. First, effects of individual elements such as S, Pt, and Cr, and reactive elements (REs) Hf, Zr, and Y, on the work of separation, Wsep, of the interface were examined. As expected, the segregation of S to the interface significantly degrades the adhesion, while the substitution of Pt for Ni adjacent to the interface does not enhance the Wsep. Cr and RE addition to the interface individually result in a considerable increase of Wsep. Second, the addition of Pt, Hf, and Cr to the S containing interface is shown to mitigate the detrimental effect of sulfur to some extent. Co doping the interface with a selected combination of (Pt, Hf), (Pt, Cr), (Cr, Hf), (Cr, Y), (Hf, Y), and (Y, Zr) was implemented to probe possible synergistic interactions between elements on Wsep. Synergistic effects are detected on increasing Wsep for (Hf, Y), (Hf, Zr) combinations. Co doping the interface with (Cr, Y) and (Cr, Hf), however, is found to weaken the adhesion. Through a detailed analysis of electronic structures in terms of ELF and DOS, four dominant bonds across the interface, RE-O, RE-Ni, Aloxide-Ni, and AlNiAl-O, are identified to play a decisive role in governing the adhesive strength of the interface.