Due to antimicrobial resistance, current treatments for tuberculosis (TB) are very limited and have very low efficacy. Existing therapeutics are inadequate for the ongoing epidemic of drug resistance TB. The evolutionary push of mutations created is destabilizing global TB control, thereby needing new novel therapies for treatment and screening purposes. In this paper, we propose two potential pathways that target TB through IFN-I signaling and the AhR pathway which allows for more accurate and efficient early screening of TB. Targeting these pathways impacts TB outcome by increasing treatment efficacy and strengthening host defense. IFN-I signaling and the AHR pathway can be seen as potential targets for host directed therapies.