BACKGROUND: Public health concerns relating to international investment liberalization have centred on the potential for investor-state dispute settlement (ISDS)-related regulatory chill. However, the broader political and economic dimensions that shape the relationship between the international investment regime and non-communicable disease (NCD) policy development have been less well explored. This review aimed to synthesise the available evidence using a political economy approach, to understand why, how and under what conditions transnational corporations may use the international investment regime to promote NCD prevention policy non-decisions. MAIN BODY: Methods: Mechanisms explaining why/how the international investment regime may be used by transnational health-harmful commodity corporations (THCCs) to encourage NCD prevention policy non-decisions, including regulatory chill, were iteratively developed. Six databases and relevant grey literature was searched, and evidence was extracted, synthesized and mapped against the various proposed explanatory mechanisms. FINDINGS: Eighty-nine sources were included. THCCs may be incentivised to use the ISDS mechanism since the costs may be outweighed by the benefits of even just delaying regulatory adoption, particularly since the chilling effect tends to ripple out across jurisdictions. Drivers of regulatory chill may include ambiguity in treaty terms, inconsistency in arbitral rulings, potential arbitrator bias and the high cost of arbitration. Evidence indicates ISDS can delay policy adoption both within the country directly involved but also in other jurisdictions. Additionally, governments are adopting standard assessments of public health regulatory proposals for trade and ISDS risk. Various economic, political and industry-related factors likely interact to increase (or decrease) the ultimate risk of regulatory chill. Some evidence indicates that THCCs take advantage of governments' prioritization of foreign investment over NCD prevention objectives to influence the NCD prevention regulatory environment. CONCLUSIONS: While ISDS-related regulatory chill is a real risk under certain conditions, international investment-related NCD prevention policy non-decisions driven by broader political economy dynamics may well be more widespread and impactful on NCD regulatory environments. There is therefore a clear need to expand the research agenda on investment liberalization and NCD policy beyond regulatory chill and engage with theories and approaches from international relations and political science, including political economy and power analyses.