<p>Over the past decade, consumer wearable sensors have become increasingly ubiquitous in health monitoring, enabling the widespread tracking of key biophysical parameters. The transition towards next-generation body-interfaced biomolecular sensing technologies, fuelled by the integration of reagentless sensing strategies with advanced nanomaterials, marks the next substantial leap forward. These innovations enable unobtrusive, multimodal monitoring of both physiological parameters and biochemical disease markers in real time. This Review examines the current generation of body-interfaced biomolecular sensing technologies, with a particular emphasis on materials innovation and nanotechnological advancements, and discusses their pivotal role in chronic disease monitoring. The discussion extends to the challenges and prospects in this rapidly evolving field, highlighting the potential for materials-focused approaches to transform the landscape of chronic disease monitoring and management with body-interfaced bioelectronics. By harnessing the power of materials and nanotechnological innovations, these biomolecular sensing technologies promise to enhance diagnostic capabilities and foster a more proactive, personalized approach to combating these diseases.</p>