ZnO-CuO flower-like hetero-nanostructures were successfully prepared by combining hydrothermal and dip coating methods. Flower-like hetero-nanostructures of ZnO-CuO were examined by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and UV-Vis. The sensing properties of ZnO-CuO flower-like hetero-nanostructures to volatile organic compounds (VOCs) were evaluated in a chamber containing acetone or isopropanol gas at room temperature. The sensitivity of ZnO-CuO flower-like hetero-nanostructures to VOCs was enhanced compared to that of pure leafage-like ZnO nanostructures. Response and recovery times were about 5 s and 6 s to 50 ppm acetone, and 10 s and 8 s to 50 ppm isopropanol, respectively. The sensing performance of ZnO-CuO flower-like hetero-nanostructures was attributed to the addition of CuO that led to formation of p-n junctions at the interface between the CuO and ZnO. In addition, the sensing mechanism was briefly discussed.