Extended respiratory panels have been limited to specific patient populations due to cost and inconclusive clinical utility. Customizing syndromic panels offers a way to balance clinical utility and available resources. In this study, we evaluated strategies and assessed the value of flexible, customized respiratory panels. A total of 200 specimens from symptomatic patients (December 2023 to September 2024), negative for SARS-CoV-2/Flu/RSV, were tested with the LIAISON PLEX Respiratory Flex Assay-an extended respiratory panel that offers flexibility in target selection. The study assessed additional diagnoses, correlations with institutional and state-wide pathogen prevalence, and whether customizable panels could optimize diagnostic yield. Sixty-two samples (31%) negative for SARS-CoV-2/Flu/RSV tested positive for other targets, primarily rhinovirus/enterovirus (60%), correlating with local and state prevalence. Weighted estimates for 18,373 symptomatic patients during the study period modeled a prevalence of 14.3% for rhinovirus/enterovirus, followed by HPIV-3, adenovirus, and coronavirus. During the study period, 6% of patients received the standard of care extended respiratory panel order after a negative SARS-CoV-2/Flu/RSV result, duplicating SARS-CoV-2/Flu/RSV testing. Leveraging a flexible feature could have resulted in an estimated staff time reduction of 5,545 minutes for a second swab collection and running a second test, in addition to the cost of running two different panels during a single encounter. Local respiratory pathogen prevalence data can guide target selection in customized panels. The inclusion of high-prevalence targets can increase the likelihood of diagnosis from 12% to nearly 30%. Flexibility in customizing targeted pathogen panels could enhance diagnostic value while conserving institutional resources.IMPORTANCERapid and accurate identification of pathogens causing respiratory tract infections can aid in guiding treatment decisions, reducing healthcare costs, and supporting real-time surveillance of infectious diseases within a community. Limitations of clinical utility beyond SARS-CoV-2/Flu/RSV are primarily driven by cost and the lack of specific treatment options. There is a need to balance clinical gaps with testing cost and diagnostic stewardship. In this study, we evaluated the utility of flexible, customized respiratory viral panels and reportable targets within a broader set of available targets in an extended respiratory panel.