Directed self-assembly (DSA) of block copolymers is an effective method to pattern dense arrays of features with dimensions in the nanoscale. The implementation of a chemo-epitaxy flow on 300 mm wafers has allowed the investigation of multiple materials and processing conditions that define a large parameter space in which to optimize DSA for commercially relevant process windows and levels of defectivity. The fabrication of chemically nanopatterned substrates in an all-track process using 193 nm immersion tools provided 14 nm half-pitch line-and-space patterns with an exposure latitude of 35% and depth of focus > 200 nm. Key parameters such as the width of the preferential-wetting guiding stripes and background chemistry of the lithographically-defined chemical patterns govern the process latitude and pattern perfection. Advances in full-wafer metrology and identification of sources of defects resulted in a better understanding of the quality of the chemical patterns and therefore the quality of the structure of the assembled block copolymer. This work provides guidelines for the most impactful pathways to follow in the development of materials and processes to minimize the number of defects using DSA of BCP for high volume manufacturing.