We report on a new strategy to synthesize Al/CuO nanothermites from commercial Al and ultra-small chemically synthesized CuO nanoparticles coated with alkylamine ligands. These usual ligands stabilize the CuO and prevent them from aggregation, with the goal to enhance the interfacial contact between Al and CuO particles. Using a variety of characterization techniques, including microscopy, spectroscopy, mass spectrometry and calorimetry (ATG/DSC), the structural and chemical evolution of CuO nanoparticles stabilized with alkylamine ligands are analyzed upon heating. This enables us to depict the main decomposition processes taking place at the CuO surface at low temperature (< 500 °C): the ligands fragment into organic species accompanied with H2O and CO2 release, which promotes the CuO reduction into Cu2O and further Cu. We quantitatively discuss these chemical processes highlighting for the first time the crucial importance of synthesis conditions that control the chemical purity of the organic ligands (octylamine molecules and derivatives such as carbamate and ammonium ions) on the nanothermite performances. From these findings, an effective method to overcome the ligands-induced CuO degradation at low temperature is proposed and Al/CuO nanothermite reaction is analyzed, in terms of onset temperature and energy released. We produce original structures composed of aluminium nanoparticles embedded in CuO grainy matrixes exhibiting onset temperature ~200 °C below usual Al/CuO onsets, having specific combustion profiles depending on synthesis conditions, while preserving the total amount of energy released.