Background: Patients with latent tuberculosis infection are mainly asymptomatic, but they still carry a notable risk of developing active TB, particularly when the host becomes immunosuppressed. Hence, appropriate diagnosis and management for LTBI are essential. Tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) are among the most commonly utilized methods for detecting LTBI. Until now, no agreement has been established regarding the most effective diagnostic test, either TST or IGRA, so our study aims to evaluate the diagnostic utility of TST versus IGRA in detecting LTBI. Methods: An extensive literature search was executed in several databases from inception till June 2024. We included all the available studies that compared TST versus IGRA concurrently applied to the same study participants, utilizing one of the following proxy reference standards: previous contact with a tuberculosis patient, tuberculosis history, chest x-ray suggestive of tuberculosis, or a combination of them. The sensitivity (SN) and specificity (SP) were imputed with their 95% confidence interval (CI). A bivariate random-effects model within the OpenMeta-Analyst software was utilized for data analysis. Results: We included 39 studies, and our primary analysis regarding LTBI revealed that TST has an SN of 0.320 (95% CI [0.254–0.393]) and an SP of 0.808 (95% CI [0.752–0.854]). Nevertheless, the IGRA exhibited a higher SN estimated at 0.362 (95% CI [0.295–0.434]) and a lower SP estimated at 0.758 (95% CI [0.700–0.808]). Regarding the adult population, TST consistently showed a lower SN and a higher SP relative to IGRA. However, within the pediatric population, TST showed higher SN and lower SP when compared to IGRA. Furthermore, TST also showed a lower SN and a higher SP within hemodialysis and organ transplant patients than IGRA. Conclusions: Our diagnostic test meta-analysis revealed that TST was associated with a lower SN and a higher SP than IGRA. Clinicians should interpret these findings with caution, considering the substantial heterogeneity observed across the included studies, the reliance on proxy reference standards, the potential influence of BCG vaccination status, and the considerable overlap in confidence intervals between TST and IGRA estimates across most analyses.