In this study, high energy materials (HEMs) derived from 1,2,4-triazolo[3,4-d]-1,2,4-triazolo[3,4-f]furazano[3,4-b]pyrazine (TTFP) substituted with –NH2, –NHNO2, –ONO2, –NO2, and –N3 explosophoric groups were designed and computationally characterized. It is found that the TTFP is an effective molecular backbone for improving the energy content and energetic performance of the designed compounds. The effect of various explosophoric groups on energy content, density, detonation performance, and sensitivity was investigated. The energetic evaluation indicated that TTFP derivatives having –NHNO2, –ONO2, and –NO2, groups demonstrate good detonation performances and exceed the performance of TNT and RDX. Considering the energetic properties, the TTFP backbone can be regarded as an energy-rich unit, which can be substituted with suitable explosophoric groups for constructing HEMs.