Innovative eHealth technologies are becoming increasingly common worldwide, with researchers and policy makers advocating their scale-up within and across health care systems. However, examples of successful scale-up remain extremely rare. Although this issue is widely acknowledged, there is still only a limited understanding of why scaling up eHealth technologies is so challenging. This article aims to contribute to a better understanding of the complexities innovators encounter when attempting to scale up eHealth technologies and their strategies for addressing these complexities. We draw on different theoretical perspectives as well as the findings of an interview-based case study of a prominent remote patient monitoring (RPM) innovation in the Netherlands. Specifically, we create a cross-disciplinary theoretical framework bringing together 3 perspectives on scale-up: a structural perspective (focusing on structural barriers and facilitators), an ecological perspective (focusing on local complexities), and a critical perspective (focusing on mutual adaptation between innovation and setting). We then mobilize these perspectives to analyze how various stakeholders (n=14) experienced efforts to scale up RPM technology. We provide 2 key insights: (1) the complexities and strategies associated with local eHealth scale-up are disconnected from those that actors encounter at a broader level scale-up, and this translates into a simultaneous need for stability and malleability, which catches stakeholders in an impasse, and (2) pre-existing circumstances and associated path dependencies shape the complexities of the local context and facilitate or constrain opportunities for the scale-up of eHealth innovation. The 3 theoretical perspectives used in this article, with their diverging assumptions about innovation scale-up, should be viewed as complementary and highlight different aspects of the complexities perceived as playing an important role. Using these perspectives, we conclude that the level at which scale-up is envisaged and the pre-existing local circumstances (2 factors whose importance is often neglected) contribute to an impasse in the scale-up of eHealth innovation at the broader level of scale.