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Electronic cigarettes (e-cigarettes), or vapes, deliver aerosols containing nicotine and other harmful chemicals. Growing evidence of health risks and international variation in regulatory policies create challenges for healthcare professionals (HPs) in providing patient information, prescribing cessation products, and ensuring safety. This review examines the roles, perceptions, and interventions of HPs regarding e-cigarettes. We searched MEDLINE (Ovid), Embase (Elsevier), CINAHL (EBSCOhost), and Web of Science for English-language studies published since 2000 that examined HPs’ knowledge, attitudes, and clinical practices related to vaping. Searches were completed on 3 October 2024. Of 1,070 records identified, 94 met the inclusion criteria. Data were analysed descriptively and synthesized narratively. Most studies were from the United States (n = 48, 51.1%), Australia (n = 13, 13.8%), and the United Kingdom (n = 12, 12.8%). More consumers were included in studies as participants compared to HPs (71,356 vs. 24,538 participants). Physicians comprised the majority of HPs (n = 15,603, 63.6%), followed by mixed clinician groups (n = 4,589, 18.7%) and nurses (n = 2,585, 10.5%). Most studies reported on HP perceptions (n = 74/94, 78.8%) followed by attitudes (n = 67/94, 71.3%), knowledge (n = 63/94, 67.0%) and clinical practices (n = 60/94, 63.8%). Screening practices were reported in 27 studies, with rates ranging from 0% to 75%. Counselling practices were addressed in 29 studies, and prescribing of e-cigarettes for smoking cessation in 34 studies. Research work outside the US, Australia, and the UK is limited. The earliest publications began in 2014, peaking in 2016 and 2022, which may reflect increased e-cigarette use as a smoking cessation tool, access, advertising, and policy changes. Pharmacists and dentists were underrepresented despite their roles in the supply of e-cigarettes and oral health. Perspectives of other allied health professionals and healthcare assistants remain largely unexplored. Screening, counselling, and prescribing e-cigarette practices varied substantially across countries, professions, and patient groups. HPs’ roles, perceptions, and interventions regarding e-cigarettes differed by country and profession. Further research should include the perceptions and interventions of a broader range of HPs and examine legislative developments and changes in guidelines across different countries, and how these impact clinical practices. These insights are essential for developing evidence-based practice standards to guide HPs in managing e-cigarette use among patients.