The interface layer is responsible for the outward migration of oxygen atoms, which subsequently leads to an adjustment in the energetic performance of nanothermite films. In this study, sandwich-structured CuO@Ni/Al and CuO@NiO/Al nanowire thermite films were successfully prepared to investigate the effects of the interface layer on the heat-release, ignition, and combustion performance. The effects of the Ni and NiO interface layers are extremely different on the heat-release performance and combustion properties of the CuO/Al nanowire thermite film. Herein, the introduced Ni layer decreased the heat release (1979.7 J/g), reactivity (Ea = 177.3 kJ/mol), and maximum pressure (2.32 MPa) compared with the CuO/Al composite. Al/Ni alloys can be formed at the interface to prevent oxygen from diffusing between CuO and Al. Moreover, the incorporation of the Ni interface layer into the CuO/Al systems results in a heat drop due to its heat-absorption capability as well as its blockage of heat transfer from the thermite reaction. The deposition of the NiO layer between CuO and Al leads to an increase in the heat release (3014.2 J/g) and a decrease in the activation energy (Ea = 178.6 kJ/mol). The NiO layer endows the CuO/Al system with a high energy-release rate and chemical reactivity. NiO can participate in a thermite reaction, which promotes the reaction of CuO/Al and induces the condensed phase.