This paper is focused on the sol-gel synthesis and characterization of CuO-based nanosystems both in the form of supported films and as guest nanoclusters embedded in a silica matrix. In both cases copper acetate (Cu(CH3COO)2 · H2O) was used as Cu source and, for the CuO :SiO2 nanocomposite systems, tetraethoxysilane (Si(OC2H5)4, TEOS) was adopted as silica precursor. Films were obtained by a dip-coating procedure and subsequently treated in air between 100 and 900°C. The system evolution on thermal annealing was studied by X-ray photoelectron spectroscopy (XPS), Glancing-Incidence X-ray diffraction (GIXRD) and optical absorption. Irrespective of the processing conditions, the formation of tenorite (CuO) crystallites with nanometric dimension was observed. In the nanocomposite samples, copper was homogeneously distributed in the host matrix and stable CuO nanoclusters (φ ≈ 15 nm) were obtained.