Here we sought to tackle the challenges of targeted methylation sequencing taking advantage of Twist’s high quality oligo synthesis, capture solutions, and the data-driven methods that have enabled very high uniformity panels. Using Twist’s newly developed methylation-specific baseline design algorithm and targeted methylation sequencing protocol, we demonstrate high performance metrics for panels of varying sizes.Using the data and responses learned, we implement optimized default design capabilities with different levels of stringency. While arrays are still widely used in methylation detection, high quality target enrichment panels provide an attractive alternative to static array designs for exploring dynamic and cell-specific methylation targets or poorly understood targets found in more elusive non coding regions at single base pair resolution.