Biomedical electronic devices integrated with specific human body parts have attracted considerable attention because they present significant breakthroughs to solve various clinical challenges. Recent innovations in soft nanomaterial assemblies, novel device design strategies, and clinically relevant system-level applications have accelerated the rapid growth in this research field. In particular, novel biomedical functionalities, such as extraordinary sensitivity in diagnosis and outstanding therapy performance, could be achieved through wearable, implantable, and minimally invasive bioelectronics. Monolithic integration of functional nanomaterial assemblies with flexible and stretchable device platforms has enabled these breakthroughs. This review first presents a brief history and then provides more details of recent advancements in nanomaterial assemblies and their applications to soft bioelectronics. Important technological advances to solve unmet clinical challenges are presented by leveraging soft bioelectronics toward the next-generation medical systems.