Current surveillance focuses on well characterized pathogens such as influenza. Since 2000, there have been multiple outbreaks of respiratory disease. These outbreaks have demonstrated the need for robust and collaborative global efforts to identify, monitor, and contain novel respiratory viruses. This study aims to improve the ability of public health agencies to monitor and respond to respiratory disease outbreaks. Using five respiratory pathogens, this study compares a molecular capture technology from Twist Biosciences to the shotgun sequencing approach of whole transcriptome amplification (WTA, Qiagen) with the goal of determining which method is most effective using cost, usability, and sequencing quality metrics for evaluation. Twist, though more expensive, had a 92.1% positive identification of targets on successful sequencing runs with greater depth and breadth of coverage. WTA failed to sequence and identify targets except Human Adenovirus 7, proving that Twist is more reliable and efficient in this study.