This study investigates, through a systematic review of literature, the acceptance of digital health solutions. The digitalization of the healthcare system leads to several benefits increasing quality of care, efficiency of the processes, and reducing unnecessary costs. However, most of digital technologies need to be accepted by the actors of a system to be effective because someone’s behavior toward an innovation can affect its capability to provide value through outputs and outcomes. This work facilitates the understanding of the mechanisms below innovation acceptance considering different contexts, technologies, and actors and highlighting the specific needs and behaviors that regulate them. This analysis is expected to show actors’ reaction to digital health solutions across the years, using a multifaceted approach. The implications of this research include the identification of tailored and effective strategies that must be implemented by policy-makers and practitioners to foster the entrance of digital health technologies in the healthcare.