BACKGROUND Individuals suffering from limb absence frequently experience neurological phantom and residuum pain, as well as neuromusculoskeletal disfunctions susceptible to compromise their residuum health [1]. Care providers have limited ways to diagnose these disfunctions, particularly when using the prosthesis during daily living [2]. There is a need for wearable and non-invasive diagnostic devices that can assist care providers to better assess and maintain residuum health by establishing the pathophysiological cause-and-effect relationship between prosthetic care interventions and residuum neuromusculoskeletal dysfunctions [3]. AIM This study outlines opportunities and challenges to the development of the next generation of diagnostic devices [2-4]. The specific objectives were to inform the identification, invention, and implementation phases of the Biodesign innovation process specific to diagnostic devices. METHOD This narrative review summarized first-hand observations, grey literature, and peer-reviewed publications. We included over 30 publications focusing on the assessments of residuum neuromusculoskeletal dysfunctions associated with mechanical constraints applied on the skin and topography of the tissues within the residuum as well as computational modelling of the residuum published between 2000 and 2021. We subjectively evaluated the invasiveness, comprehensiveness, and practicality of each technology deemed appropriate to be integrated into the next-generation diagnostic devices. RESULTS Our assessments of these technologies suggested that it will be feasible and worthwhile to develop user-friendly diagnostic devices that could be used safely, efficiently, and routinely by qualified clinicians at critical points of care. However, future novel diagnostic devices will have to overcome the current significant barriers associated with design (e.g., loading measurements, topography of residuum tissues during real-life activities, and computational modelling, gaps between technology readiness levels of essential parts), clinical roll-out (e.g., identification of primary user), and commercialisation (e.g., limited interest from investors inherent to niche market). Future diagnostic devices supporting the management of limb loss must sustain personalized evidence-based prosthetic care, patient empowerment and development of bionic solutions, whilst positively disrupting the organisation of healthcare by enabling cost-utility analyses required by fee-for-device business models and addressing healthcare gaps due to labour shortages. DISCUSSION AND CONCLUSION The selection of studies was biased toward systematic reviews and secondary selection of specific articles. We overlooked the strength of the methodology, level of evidence and recommendations of the selected studies. The appraisal of the potential contributions of a particular device was subjective. Nonetheless, we anticipate that the next-generation diagnostic devices will play a key role in bionic innovations that will safely increase mobility and quality of life of the growing population of individuals suffering from limb loss.