Digital health interventions (DHIs) have become essential complementary solutions in health care to enhance support and communication at a distance, with evidence of improving patient outcomes. Improving clinical outcomes is a major determinant of success in any health intervention, influencing its funding, development, adoption and implementation in real-world practice. In this article we explore our experiences of developing and testing DHIs to identify and discuss complexity challenges along their intervention research lifecycle. Informed by the case study research approach, we selected three individual DHIs aimed at satisfying the supportive and educational needs of people living with cancer. The Care Expert, the Digi-Do and the Gatapp were underpinned on different complexity frameworks i.e., the Medical Research Council framework and the Non-adoption, Abandonment, Scale-up, Spread and Sustainability framework. This variance on the methodological underpinning was expected to prompt a multifaceted discussion on the complexity dimensions endorsed by each of the frameworks. Our discussion endorses the adoption of mixed-methods research designs, to gather the perspectives of stakeholders and end-users, as well as pragmatic evaluation approaches that value effectiveness outcomes as much as process outcomes. Furthermore, the dissemination and sustainability agenda of DHIs needs to be considered from early-stage development with the inclusion of a business model. This business plan should be worked in partnership with healthcare services, regulatory bodies and industry, aiming to assure the management of the DHI throughout time.