The GeneXpert® Xpert® Xpress SARS-CoV-2/Flu/RSV PLUS combination test (PLUS Assay) received Health Canada approval in January 2022. The PLUS Assay is similar to the SARS-CoV-2/Flu/RSV combination test, with modifications to improve assay robustness against circulating and emerging variants. The performance characteristics of the PLUS Assay were assessed at the Lakeridge Health Oshawa Hospital Centre and the National Microbiology Laboratory of Canada. The PLUS Assay was directly compared to the SARS-CoV-2/Flu/RSV combination test using SARS-CoV-2 culture from five variants and remnant clinical specimens collected across the COVID-19 pandemic. This included 50 clinical specimens negative for all pathogens, 110 clinical specimens positive for SARS-CoV-2, Influenza A, Influenza B, RSVA, and/or RSVB and an additional 11 mixed samples to screen for target interactions. The PLUS Assay showed a high percent agreement with the widely used SARS-CoV-2/Flu/RSV combination test. Based on these findings, the PLUS Assay and the Xpert SARS-CoV-2/Flu/RSV combination test results are largely consistent with no observed difference in sensitivity, specificity, or time to result when challenged with various SARS-CoV-2 variants. The reported Ct values provided by the new PLUS Assay was also unchanged, with the exception of a possible 1-2 cycle decrease reported Ct for RSVA across a limited sample size.