As part of its research and development activities on high-energy X-ray imaging for nondestructive characterization, the Nuclear Measurement Laboratory has started an upgrade of its imaging system currently implemented at the CEA-Cadarache Center. The goals are to achieve a submillimeter spatial resolution and the ability to perform tomographies on very large objects (more than 100-cm standard concrete or 40-cm steel). This paper presents the results on the detection part of the imaging system. The upgrade of the detection part needs a thorough study of the performance of two detectors: a series of CdTe semiconductor sensors and two arrays of segmented CdWO4 scintillators with different pixel sizes. This paper consists of a quantum accounting diagram analysis coupled with Monte Carlo simulations. The scintillator arrays should be able to detect the millimeter details through 140 cm of concrete but are limited to 120 cm for the smaller ones. CdTe sensors have lower but more homogeneous performance, with a 0.5-mm resolution for 90 cm of concrete. The choice of the detector then depends on the preferred characteristic: the spatial resolution or the use on large volumes. The combination of the features of the source and the studies on the detectors gives the expected performance of the whole equipment, in terms of signal-over-noise ratio, spatial resolution, and acquisition time. Finally, experimental validations are carried out and validate the simulated performances.