<p>Biomolecular profiling offers a powerful lens into human physiology, yet current diagnostics often rely on invasive sampling and delayed, centralized analysis. Advances in mass spectrometry (MS), particularly untargeted metabolomics and proteomics, have expanded molecular access to noninvasive biofluids such as sweat, saliva, tears and interstitial fluid, revealing dynamic biomarkers linked to both chronic and acute conditions. In parallel, wearable biosensors enable real-time, on-body chemical sensing, but remain limited to a narrow panel of predefined analytes. This Review highlights how MS-based molecular discovery and wearable sensing serve as complementary approaches—MS enabling high-dimensional untargeted profiling and wearables delivering longitudinal real-time data—and also discusses how their bidirectional integration and co-evolution open new possibilities for personalized noninvasive health monitoring. We discuss advances in sampling strategies, sensing modalities and system integration, and outline criteria for identifying biomarkers amenable to sensor translation. By uniting untargeted discovery with real-world deployment, this convergence shifts personalized noninvasive healthcare from episodic diagnostics to continuous, context-aware monitoring.</p>