Stroke represents the third cause of long-term disability in the world. About 80% of stroke patients have an impairment of bio-motor functions and over half fail to regain arm functionality, resulting in motor movement control disorder with serious loss in terms of social independence. Therefore, rehabilitation plays a key role in the reduction of patient disabilities, and 3D printing (3DP) has showed interesting improvements in related fields, thanks to the possibility to produce customized, eco-sustainable and cost-effective orthoses. This study investigated the clinical use of 3DP orthosis in rehabilitation compared to the traditional ones, focusing on the correlation between 3DP technology, therapy and outcomes. We screened 138 articles from PubMed, Scopus and Web of Science, selecting the 10 articles fulfilling the inclusion criteria, which were subsequently examined for the systematic review. The results showed that 3DP provides substantial advantages in terms of upper limb orthosis designed on the patient's needs. Moreover, seven research activities used biodegradable/recyclable materials, underlining the great potential of validated 3DP solutions in a clinical rehabilitation setting. The aim of this study was to highlight how 3DP could overcome the limitations of standard medical devices in order to support clinicians, bioengineers and innovation managers during the implementation of Healthcare 4.0.