Nitroxides involve compounds that are extensively used in chemistry, biology, and material chemistry, especially in the area of energetic materials. In this work, novel substituent-guided synthesis of a series of high-energy-density compounds based on [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine-8-oxide (triazolotetrazine-8-oxide) was described. The inductive effect-focused N-oxidation of triazolotetrazine was demonstrated, along with its selectivity and general applicability. Electron-withdrawing groups inducing the construction of the triazolotetrazine-8-oxide skeleton were studied by theoretical methods. Additionally, a connection between the structure and the energetic performance of triazolotetrazine-based regional sites in the N–O group was determined. Among them, 3,6-dinitramino-triazolotetrazine-8-oxide (BITE-102) shows high density (2.01 g/cm³) and detonation performances (D = 10,097 m/s, P = 47.0 GPa) superior to those of the benchmark explosive CL-20 (D = 9,455 m/s, P = 46.7 GPa).