Throughout Southeast Asia, repressive drug laws have resulted in high rates of imprisonment in people who inject drugs (PWID) and people living with HIV (PLH), greatly magnifying the harm associated with HIV, tuberculosis, and addiction. We review findings from Malaysia's largest prison to describe the negative synergistic effects of HIV, tuberculosis, addiction, and incarceration that contribute to a 'perfect storm' of events challenging public and personal health and offer insights into innovative strategies to control these converging epidemics. The majority of PLH who are imprisoned in Malaysia are opioid dependent PWID. Although promoted by official policy, evidence-based addiction treatment is largely unavailable, contributing to rapid relapse and/or overdose after release. Similarly, HIV treatment in prisons and compulsory drug treatment centers is sometimes inadequate or absent. The prevalence of active tuberculosis is high, particularly in PLH, and over 80 % of prisoners and prison personnel are latently infected. Mandatory HIV testing and subsequent segregation of HIV-infected prisoners increases the likelihood of tuberculosis acquisition and progression to active disease, amplifying the reservoir of infection for other prisoners. We discuss strategies to control these intersecting epidemics including screening linked to standardized treatment protocols for all three conditions, and effective transitional programs for released prisoners. For example, recently introduced evidence-based interventions in prisons like antiretroviral therapy (ART) to treat HIV, isoniazid preventive therapy to treat latent tuberculosis infection, and methadone maintenance to treat opioid dependence, have markedly improved clinical care and reduced morbidity and mortality. Since introduction of these interventions in September 2012, all-cause and HIV-related mortality have decreased by 50.0 % and 75.7 %, respectively. We discuss the further deployment of these interventions in Malaysian prisons.