Abstract The phonon-glass electron-crystal paradigm has guided thermoelectric research in recent years. However, the inherent conflict between atomic disorder reducing phonon conduction, and the order required to maintain high electron mobility, creates a significant challenge in material design, which has driven innovation in nanostructuring and composite materials. Here, vertically aligned nanocomposites (VANs) composed of self-assembled metallic La0.7Sr0.3MnO3 (LSMO) nanopillars in a surrounding ZnO matrix are investigated for controllable thermal conductivity. Tuning of the crystal orientation of the substrate controls the epitaxial alignment of the LSMO and ZnO phases along the horizontal and vertical interfaces. The VAN films on (111)-oriented STO substrates exhibit an increased power factor of 0.52 μW·cm−1·K−2 at 600 °C beyond ZnO films of 0.15 μW·cm−1·K−2. Detailed characterization and modeling of the thermal conductivity demonstrates a reduction of about 75% as well as anisotropic behavior for the VAN films with out-of-plane and in-plane thermal conductivities of respectively 9.2 and 1.5 W·m−1·K−1, in strong contrast to the isotropic behavior in ZnO films with a thermal conductivity of 38 W·m−1·K−1. These results show the promising strategy of VAN thin films with a nanopillar-matrix architecture to scatter phonons and to enhance the thermoelectric performance.