High critical current densities (Jc) in thick films of the Y1Ba2Cu3O7–δ (YBCO, Tc ≈ 92 K) superconductor directly depend upon the types of nanoscale defects and their densities within the films. A major challenge for developing a viable wire technology is to introduce nanoscale defect structures into the YBCO grains of the thick film suitable for flux pinning and the tailoring of the superconducting properties to specific, application-dependent, temperature and magnetic field conditions. Concurrently, the YBCO film needs to be integrated into a macroscopically defect-free conductor in which the grain-to-grain connectivity maintains levels of inter-grain Jc that are comparable to the intra-grain Jc. That is, high critical current (Ic) YBCO coated conductors must contain engineered inhomogeneities on the nanoscale, while being homogeneous on the macroscale. An analysis is presented of the advances in high-performance YBCO coated-conductors using chemical solution deposition (CSD) based on metal trifluoroacetates and the subsequent processing to nano-engineer the microstructure for tuneable superconducting wires. Multi-scale structural, chemical, and electrical investigations of the CSD film processes, thick film development, key microstructural features, and wire properties are presented. Prospects for further development of much higher Ic wires for large-scale, commercial application are discussed within the context of these recent advances.