Purpose: Innovations in small and medium-sized enterprises (SMEs) are essential for increasing resource efficiency and sustainability in the agri-food system. An innovation support service (ISS) can benefit SMEs but the provision and access to it can be restricted across national borders thereby hindering cross-border regions' economic potential. The aim was to investigate how ISSs are provided and used in such a region and explore stakeholders' perceptions on their limitations and opportunities. Methodology: We conducted a case study in the Dutch-German cross-border region Euregio Rhine-Waal which included a content analysis of websites and stakeholder interviews. Findings: The provision of ISSs was limited by differing structures and priorities in both countries. SMEs' unfamiliarity with responsible authorities, significant administrative effort, and uncertainty about pay-offs were perceived as factors limiting ISS. Practical implications: We provide recommendations on how to improve ISS in cross-border regions and inform policymaking for cross-border regional development. We recommend reducing limitations of ISS provision and use, e.g. by engaging ISS providers and users in a co-creative approach. Furthermore, we suggest using opportunities of ISS provision and use, e.g. through increased promotion of available ISS by brokers. Theoretical implications: Our research contributes to the literature of extension and advisory systems by showing how differing institutional settings, combined with different 'innovation cultures' and the availability of cross-border brokers affect cross-border integration of ISS. Originality: This is the first study to explore the limitations and potentials of ISSs in a cross-border region.