HIV and tuberculosis (TB) co-infection is a significant global health challenge, requiring combination therapy with antiretroviral therapy (ART) for HIV and anti-TB drugs, which can lead to drug-drug interactions (DDIs). These interactions can affect treatment outcomes, efficacy, and patient safety. This review discusses the DDIs between anti-HIV and anti-TB drugs, potential adverse effects, and strategies for personalized treatment. HIV targets CD4+ T cells, weakening the immune response and increasing susceptibility to TB. TB, caused by Mycobacterium tuberculosis, is a slow-growing bacterium that can lead to latent TB infection, which may reactivate in HIV-positive individuals. HIV and TB co-infection requires careful management due to the complexity of treatment regimens, including ART and anti-TB medications, and the risk of DDIs. Current ART includes NRTIs, NNRTIs, INSTIs, PIs, CCR5 inhibitors, and Ibalizumab. Anti-TB treatments include first-line drugs like Rifampin, Isoniazid, Pyrazinamide, and Ethambutol, with second-line drugs for drug-resistant strains. The management of HIV-TB co-infection involves considering DDIs, dose adjustments, and alternative therapies to ensure effective treatment and minimize adverse effects. Research into novel therapeutic strategies, such as dual-targeted heterodimers and metabolite targeting, shows promise for improving outcomes in co-infected individuals. Despite advancements, challenges remain in managing HIV-TB co-infection due to drug resistance, adverse effects, and the synergistic nature of the two diseases. Effective treatment requires a comprehensive approach, including personalized care, dose adjustments, and ongoing research to address the complexities of co-infection.HIV and tuberculosis (TB) co-infection is a significant global health challenge, requiring combination therapy with antiretroviral therapy (ART) for HIV and anti-TB drugs, which can lead to drug-drug interactions (DDIs). These interactions can affect treatment outcomes, efficacy, and patient safety. This review discusses the DDIs between anti-HIV and anti-TB drugs, potential adverse effects, and strategies for personalized treatment. HIV targets CD4+ T cells, weakening the immune response and increasing susceptibility to TB. TB, caused by Mycobacterium tuberculosis, is a slow-growing bacterium that can lead to latent TB infection, which may reactivate in HIV-positive individuals. HIV and TB co-infection requires careful management due to the complexity of treatment regimens, including ART and anti-TB medications, and the risk of DDIs. Current ART includes NRTIs, NNRTIs, INSTIs, PIs, CCR5 inhibitors, and Ibalizumab. Anti-TB treatments include first-line drugs like Rifampin, Isoniazid, Pyrazinamide, and Ethambutol, with second-line drugs for drug-resistant strains. The management of HIV-TB co-infection involves considering DDIs, dose adjustments, and alternative therapies to ensure effective treatment and minimize adverse effects. Research into novel therapeutic strategies, such as dual-targeted heterodimers and metabolite targeting, shows promise for improving outcomes in co-infected individuals. Despite advancements, challenges remain in managing HIV-TB co-infection due to drug resistance, adverse effects, and the synergistic nature of the two diseases. Effective treatment requires a comprehensive approach, including personalized care, dose adjustments, and ongoing research to address the complexities of co-infection.