The digitisation of healthcare has allowed a significant rethinking of the previous clinical protocols, improving their interoperability through substantial standardisation. These technological advances have ensured that data are comparable, as they are obtained from ‘reliable’ and certified processes; however, there are billions of data that are neither structured nor quality-controlled. They are collectively referred to as ‘Real World Data’ (RWD). Blockchain (BC) is a procedure with specific characteristics and algorithms that ensure that the stored data cannot be tampered with. Nowadays, there is an increasing need to rethink blockchain in a one-health vision, making it more than just a ‘repository’ of data and information, but rather an active player in the process of data sharing. In this landscape, several scholars have analysed the potential benefits of BC in healthcare, focusing on the sharing and safety of clinical data and its contact tracing applications. There is limited research on this matter; moreover, there is a strategic interest in managing RWD in a reliable and comparable way, despite the lack of knowledge on this topic. Our work aims to analyse systematically the most impacting literature, highlighting the main aspects of BC within the context of the new digital healthcare, and speculating on the unexpressed potential of RWD.