<h3>Objectives:</h3> Recently, TMB ≥10 tumor mutational burden-high (TMB-high)mutations/megabase (mut/Mb) was approved as a companion diagnostic for pembrolizumab in patients with unresectable or metastatic solid tumor based on the KEYNOTE-158 trial. This approval offers patients with gynecologic tumors another pathway to pursue eligibility for immune checkpoint inhibitors (ICPI). Here, we present the real-world prevalence of TMB-High in a large cohort of gynecologic tumors and examine its correlation to other ICPI biomarkers. <h3>Methods:</h3> We retrospectively reviewed 17,304 gynecologic tumors tested with comprehensive genomic profiling (CGP). TMB was determined on 0.79 Mb of sequenced DNA, microsatellite instability (MSI) was assessed across 95 loci, and <i>CD274</i> amplification was defined copy number ≥ ploidy + 4. For a subset of cases, PD-L1 immunohistochemistry was performed concurrently on the samples with DAKO 22C3 assay and scored with a combined positive score (CPS) or a tumor proportion score (TPS). For cervical carcinoma, a CPS ≥ 1 was considered positive and for non-cervical carcinoma, a TPS ≥ 1 was considered positive. <h3>Results:</h3> TMB-High frequencies varied amongst the different types of gynecologic tumors, with TMB-High occurring more frequently in vaginal carcinoma, uterine carcinoma, and cervical carcinoma (27.5%, 22.1%, and 21.4%, respectively) and less frequently in vulvar carcinoma, ovarian carcinoma, fallopian tube carcinoma, and peritoneum carcinoma (10.0%, 4.0%, 3.5%, 2.0%, respectively). MSI-High was highly correlated with TMB-High, although a small subset of MSI-High was present in the cervical carcinoma and uterine carcinoma TMB < 10 mut/Mb disease subset (0.2% and 1.2%, respectively). PD-L1 positivity was also present in the TMB < 10 mut/Mb disease subset in all tumor types, ranging from 25.7% to 83.4%. <i>CD274</i> (PD-L1) gene amplification was present in the TMB < 10 mut/Mb disease subset at a low proportion in all tumor types except for vaginal carcinoma. <i>POLE</i>-mutated tumors were enriched in most gynecologic tumor TMB-High disease subsets with highest levels of mut/Mb (hypermutation, median 186 mut/Mb). Resistance (<i>STK11</i> alteration) and hyper-progression (<i>MDM2/4</i> amplifications) ICPI biomarkers established in other tumor types were present in almost all TMB disease subsets across tumor types. <h3>Conclusions:</h3> TMB-High is common in many types of gynecologic tumors and can identify additional patients that may be eligible for ICPI that are not identified by MSI, PD-L1, and <i>CD274</i> amplification ICPI biomarkers. In addition, potential resistance and hyper-progression biomarkers were present in most gynecologic tumor TMB disease subsets. These results highlight that CGP should be considered for all gynecologic tumors in order to evaluate TMB, identify <i>POLE</i>-hypermutated carcinomas, and to determine eligibility for ICPI.