Targeted sequencing remains essential in translational and clinical research, but conventional hybrid capture workflows are hindered by long hands-on time, complex reagent handling, and enrichment bias. We present a novel, automated method for targeted enrichment performed directly on the sequencing flow cell, eliminating upfront capture, amplification, and cleanup steps. This workshop will compare the performance of on-flow cell enrichment to traditional hybrid capture across multiple sequencing platforms. Results highlight faster time-to-results, fewer manual steps, and improved reproducibility. In addition, higher library complexity and more uniform coverage is observed, enhancing variant detection accuracy. Implementation data from an active user site will also be shared, including comparisons to existing pipelines and considerations for technology adoption.