Background: Tumor Treating Fields (TTFields) are electric fields that exert forces on cancer cells, disrupting processes critical for cancer cell viability and tumor progression. TTFields therapy became an FDA-approved treatment option for patients with newly diagnosed glioblastoma (GBM) in 2015 on the basis of the randomized controlled EF-14 study (NCT00916409). Subsequent approvals worldwide and increased adoption of TTFields has led to the question of whether or not a consistent survival benefit has been observed in the real-world setting, and whether device usage has played a role. Methods: A literature search was conducted using PubMed, Embase, and the Cochrane Library to identify clinical studies evaluating overall survival in adult patients with GBM treated with TTFields therapy. Comparative studies and single-cohort studies reporting on survival outcomes were included in the analysis. Inter-study heterogeneity was assessed using the Cochran Q test and quantified using the Higgins I² statistic. Survival curves were pooled using a distribution-free random-effects method. Results: Our review identified 8 studies evaluating the clinical efficacy of TTFields therapy in newly diagnosed GBM, with patients spanning diverse geographic regions. Of these 8, 6 studies (reporting on a total of 1378 patients) compared the addition of TTFields therapy to standard of care (SOC) vs SOC alone, and were included in a pooled analysis for overall survival. Meta-analysis of comparative studies indicated a significant improvement in overall survival for patients treated with TTFields therapy vs those not receiving treatment (hazard ratio [HR]: 0.62; 95% CI, 0.52–0.73; P< 0.001). Inter-study heterogeneity was examined, and a sensitivity analysis indicated the pooled effect was robust and not dependent on any individual study. Among post-approval studies, the pooled median overall survival was 22.2 months (95% CI, 17.3–42.6) for TTFields-treated patients and 17.3 months (95% CI, 13.6–22.0) for the non-TTFields group. Rates of gross total resection were generally higher in the real-world setting, irrespective of TTFields use. Furthermore, among studies reporting data on TTFields device usage, an average device usage rate of 75% or higher was found to consistently associate with prolonged survival when compared to an average usage rate below 75% (pooled HR: 0.63; 95% CI, 0.48–0.83; P = 0.001). Conclusions: Meta-analysis of comparative studies suggests a significant survival benefit with TTFields therapy added to standard radiochemotherapy for patients with newly diagnosed GBM, and that a 75% usage rate may be meaningful in the real-world setting.