Infection of artificial urinary sphincters or inflatable penile prostheses is one of the most devastating complications after prosthetic surgery and can have a significant impact on a quality of life. Patients undergoing revision surgery with or without device replacement may have increased risk for infection when compared to initial primary surgery. As such, surgeons may utilize traditional culture results to direct antimicrobial therapy for these patients. Unfortunately, culture results can be inconclusive in up to one-third of the time even in the setting of active device infection. Next-generation sequencing (NGS) of DNA is an emerging technology capable of sequencing entire bacterial genomes and has the potential to identify microbial composition in explanted devices. Herein, we describe our institutional experience on NGS utilization in patients with genitourinary prostheses. We also highlight our methods and techniques to inform readers on the potential practices that can enhance the utility and diagnostic yield of this new and upcoming technology.