Explosive compositions employing nanoscale crystals of high explosives (i.e., nanoenergetics) have demonstrated reduced sensitivities to external stimuli. Until recently, the investigated formulations were limited to plastic bonded explosives. Explosives that are normally melt-cast also would benefit from the use of nanoenergetics. However, the integration of nanoenergetics into the melt-cast process is challenging due to the large surface area and solubility associated with nanoenergetics. In this work, we explored the preparation of nanoenergetics-based Composition B (Comp B), a widely used melt-cast explosive, by spray drying followed by mechanical compaction. The Comp B molding powder obtained from spray drying was characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The structure and the shock sensitivity of the compacted nanoenergetics-based Comp B (N-Comp B), both as-prepared and thermally cycled, was also studied using melt-cast Comp B as the reference material. The characterization shows that N-Comp B consisting of nanoscale cyclotrimethylenetrinitramine (RDX) and trinitrotoluene (TNT) contains mostly nanoscale voids but has a large number density. Reduced shock sensitivity was observed from NComp B, attributed to the elimination of large voids. But the decrease seems to have been constrained by the large number density of voids. Thermal cycling induced significant structural change, i.e., the increase of both void size and the crystal size, causing an increase in sensitivity. Procedures are proposed to further reduce the sensitivity and enhance the thermal stability of N-Comp B.