Semiconductors hold great promise for surface-enhanced Raman scattering (SERS) applications. Various strategies have been proposed to address the challenge of low SERS sensitivity in semiconductors, with the construction of heterojunctions being among the most effective approaches. In this study, CuO@TiO2 heterojunctions were fabricated by depositing a precisely controlled layer of TiO2 film onto the surface of CuO nanowires (CuO NWs) using the atomic layer deposition (ALD) technique. This approach significantly enhances the SERS sensitivity of CuO NWs, and the SERS performance of the semiconductor heterojunction can be further optimized by accurately adjusting the thickness of TiO2. The SERS activity exhibits systematic variations with the TiO2 thickness across the CuO@TiO2-Rhodamine 6G (R6G) system, with the optimal SERS performance of the heterojunction substrate achieved at a TiO2 thickness of 250 cycles. This finding highlights the substantial influence of TiO2 coating thickness on the photo-induced charge transfer (PICT) processes within the CuO@TiO2-R6G system. Furthermore, CuO@TiO2 heterojunctions demonstrate exceptional stability and uniformity. As a result, this study holds significant importance in enhancing the SERS performance of oxide semiconductors, designing optimal semiconductor heterojunction SERS substrates, and investigating thickness-dependent charge transfer mechanisms in semiconductors.