Treatment for human tuberculosis (TB) and other granulomatous diseases would benefit from high- throughput screening (HTS)-compatible platform replicating physiological conditions in hallmark granuloma lesions. However, currently available screening platforms and 2-D and 3-D cell culture systems lack throughput and key features, and relevant microenvironments present in human TB granulomas, such as the formation of well-organized tuberculoma structure, granuloma lesions, biochemical and physiological gradients, diverse forms, and development of features like enhanced central hypoxia, necrosis, acidosis, and cavity formation. This technology is for bioengineering an HTS-compatible and shelf-stable in vitro tuberculoma bioplatform similar to human tuberculous granuloma lesions for rapid screening of pathogen-targeted and host-directed compounds and other therapeutics against the mycobacterial strains causing TB. This robust 3-D bioplatform exhibits the key attributes and microenvironments of human TB granuloma lesions. The bioplatform can be used to investigate host-pathogen interactions and trained immunity against mycobacterial infections and identify and characterize antimicrobial therapeutics, biologics, and immunotherapies against TB, other mycobacterial diseases, and associated co-infections and morbidities. This tool can accelerate drug discovery efforts and translational advances against various granulomatous diseases.