The present disclosure relates to a method of manufacturing a nanowire structure. According to an exemplary process, a substrate is firstly provided. An intact buffer region is formed over the substrate, and a sacrificial top portion of the intact buffer region is eliminated to provide a buffer layer with a planarized top surface. Herein, the planarized top surface has a vertical roughness below 10 Å. Next, a patterned mask with an opening is formed over the buffer layer, such that a portion of the planarized top surface of the buffer layer is exposed. A nanowire is formed over the exposed portion of the planarized top surface of the buffer layer through the opening of the patterned mask. The buffer layer is configured to have a lattice constant that provides a transition between the lattice constant of the substrate and the lattice constant of the nanowire.