Conformable bioelectronic systems are promising tools that may aid the understanding of diseases, alleviate pathological symptoms such as chronic pain, heart arrhythmia, and dysfunctions, and assist in reversing conditions such as deafness, blindness, and paralysis. Combining reduced invasiveness with advanced electronic functions, hybrid bioelectronic systems have evolved tremendously in the last decade, pushed by progress in materials science, micro- and nanofabrication, system assembly and packaging, and biomedical engineering. Hybrid integration refers here to a technological approach to embed within mechanically compliant carrier substrates electronic components and circuits prepared with traditional electronic materials. This combination leverages mechanical and electronic performance of polymer substrates and device materials, respectively, and offers many opportunities for man-made systems to communicate with the body with unmet precision. However, trade-offs between materials selection, manufacturing processes, resolution, electrical function, mechanical integrity, biointegration, and reliability should be considered. Herein, prominent trends in manufacturing conformable hybrid systems are analyzed and key design, function, and validation principles are outlined together with the remaining challenges to produce reliable conformable, hybrid bioelectronic systems.