Evidence suggests telehealth can be cost-effective and improve outcomes, including in cross-jurisdictional settings. We examined how cross-border telehealth could support health system transformation and consulted experts to identify priority policy considerations for integrating services across jurisdictions. We conducted a multimethod policy analysis comprising a narrative review informed by targeted searches and policy mapping, pre-Delphi working-group discussions, and a three-round modified Delphi consensus process with 18 experts in health policy, health-care regulation, telehealth implementation and international trade. We then made our draft findings available for World Health Organization-hosted public consultation, incorporating feedback and updating our narrative review. Our finalized challenge-policy matrix included 20 key challenges that we categorized within seven domains: knowledge and awareness; policy and governance; technology and operational issues; data security and privacy; quality and ethical standards; financial and economic factors; and adaptability and resilience. In our detailed challenge-policy matrix we identify national and international required policy actions for all 20 key challenges, which we summarize as: reinforce regulatory frameworks and international commitments; strengthen governance and coordination; build digital health capacity; ensure data privacy and security; and promote sustainable financing models. From a public health perspective, cross-border telehealth is essential for the strengthening of global health systems. Tackling the challenges of regulatory heterogeneity, exclusion from international trade agreements, digital literacy, language barriers and financial constraints requires that regulatory, technological and operational constraints be addressed through international policy cooperation. Priorities include interoperable regulatory frameworks, reduction or removal of unnecessary barriers, infrastructure investment, data protection, sustainable financing and emergency preparedness.