Tuberculosis, caused by Mycobacterium tuberculosis, remains a global burden on our country and entire world. According to the World Health Organization, 10 million incident cases of tuberculosis were registered in 2019. A steady increase in the drug-resistant tuberculosis aggravates the situation and appears to be the major obstacle to the fight against the disease. A thorough understanding of the pathogen physiology and virulence properties is extremely important for the development of new diagnosis methods and treatment strategies. Multiomics approaches to studying the infectious agents are indispensable in understanding the nature of the disease. Despite the availability of sufficient genomic and transcriptomic data, pathogenic potential, survival rate, persistence, immunomodulation, mechanisms underlying drug resistance and host–pathogen interaction remain poorly understood. The use of proteomic approaches has been more informative, and provides more information about the true state of the cell in various conditions. Proteomic and bioinformatic approaches helped considerably in identification and characterization of target proteins that could be used for the development of new therapeutic options. Nevertheless, OMICs data integration with simultaneous use of the system approach to studying various clinically significant mycobacterial strains makes it possible to increase knowledge about the disease mechanisms and infection control methods. The review outlines various OMICs technologies and their role in the development of the M. tuberculosis diagnostic panels.