Background: In 2023, tuberculosis (TB) caused 1.25 million deaths globally, remaining a leading infectious killer. Central Asia and Southern Caucasus face high TB burdens, particularly Mongolia. This review synthesizes TB prevalence data and diagnostic capabilities in these regions to support public health strategies. Methods: This systematic review aimed to synthesize current data on TB prevalence in Central Asia, Southern Caucasus, and Mongolia to support public health strategies and research priorities. A comprehensive search of PubMed and Google Scholar was conducted for English-language articles published up to 2023. Studies were assessed using a modified Newcastle–Ottawa Scale. Nine studies met the inclusion criteria, covering Kazakhstan, Kyrgyzstan, Uzbekistan, Tajikistan, Turkmenistan, Mongolia, Georgia, Armenia, and Azerbaijan. Results: TB incidence ranged from 67 per 100,000 in Kazakhstan to 190 per 100,000 in Kyrgyzstan, with the highest prevalence of 68.5% in Mongolia. TB affected men more frequently (65.3%), and the key risk factors included HIV (30.5%), comorbidities, and undernutrition. Diagnostic performance varied significantly (microscopy sensitivity, 45–65%; GeneXpert MTB/RIF, 89–96% sensitivity and 98% specificity for rifampicin resistance). Diagnostic turnaround times ranged from hours (molecular) to weeks (conventional). Only 58% of TB facilities had GeneXpert technology, with urban–rural disparities in diagnostic access. Drug-resistant TB imposed a significant economic burden, with treatment costs ranging from USD 106 to USD 3125. Conclusions: Strengthening surveillance, improving data collection, and conducting longitudinal studies are essential for designing effective TB control strategies in these regions. Significant diagnostic gaps persist across these regions, especially with regard to drug-resistant strains. Point-of-care molecular diagnostics, improved algorithms, and expanded laboratory training show promise. Future research should focus on rapid biomarker-based diagnostics, field-deployable technologies for settings with limited resources, and AI integration to enhance diagnostic accuracy and efficiency.