Biological approaches for the synthesis of a hybrid explosive–nanothermite energetic composite have attracted greater scientific attention because of their advantages, including their moderate reactions and the absence of secondary pollution. In this study, a simple technique was developed to fabricate a hybrid explosive–nanothermite energetic composite based on a peptide and a mussel-inspired surface modification. Polydopamine (PDA) was easily imprinted onto the HMX, where it maintained its reactivity and was capable of reacting with a specific peptide used to introduce Al and CuO NPs to the surface of the HMX via specific recognition. The hybrid explosive–nanothermite energetic composites were characterized using differential scanning calorimetry (TG-DSC), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy(XPS), and a fluorescence microscope. A thermal analysis was utilized to investigate the energy-release properties of the materials. The HMX@Al@CuO, which benefitted from an enhanced interfacial contact in comparison with the physically mixed sample (HMX-Al-CuO), demonstrated a 41% lower HMX activation energy.