Background: Opioids are essential medicines. Despite international and national laws permitting availability, opioid access remains inadequate, particularly in South, Southeast, East and Central Asia. Aim: To review evidence of perceptions and experiences of regulatory enablers and barriers to opioid access in South, Southeast, East and Central Asia. Design: Systematic review of post-2000 research according to PRISMA guidelines. Data were subjected to critical interpretive synthesis. International, national and sub-national barriers were organised developing a conceptual framework of opioid availability. Data sources: PsycINFO, Medline, Embase, The Cochrane Library. CINAHL, Complete and ASSIA from 2000 until 20th May 2019. Results: 21/14097 studies included: quantitative n = 15, qualitative n = 3 and mixed-methods n = 3. Four barrier/enabler themes were developed: Legal, regulatory, socio-political; lack of laws explicitly enabling opioid access, restrictive international controls and clinician prescribing concerns. Opioid availability; limited availability, poor policymaker and clinician education regarding opioid benefits, poor continuity of supply. Opioid Accessibility; medicine costs, distance to prescribing centres. Prescribing; extensive bureaucratic barriers, lack of human resources for prescribing. We present a novel framework of a self-perpetuating model of inadequate opioid provision. The Single Convention on Narcotics provides the context of restrictive laws and negative attitudes amongst policymakers. A consequent lack of prescribers and clinicians’ negative attitudes at sub-national levels, results in inadequate access to and use of opioids. Data of inadequate consumption informs annual requirement estimates used by the International Narcotics Control Board to determine future opioid availability. Conclusions: Regulatory and socio-political actions unintentionally limit opioid access. International and national laws explicitly enabling opioid access are required, to assuage concerns, promote training and appropriate prescribing.