Point-of-care (POC) has the capacity to support low-cost, accurate and real-time actionable diagnostic data. Microneedle sensors have received considerable attention as an emerging technique to evolve blood-based diagnostics owing to their direct and painless access to a rich source of biomarkers from interstitial fluid. This review systematically summarizes the recent innovations in microneedle sensors with a particular focus on their utility in POC diagnostics and personalized medicine. The integration of various sensing techniques, mostly electrochemical and optical sensing, has been established in diverse architectures of "lab-on-a-microneedle" platforms. Microneedle sensors with tailored geometries, mechanical flexibility, and biocompatibility are constructed with a variety of materials and fabrication methods. Microneedles categorized into four types: metals, inorganics, polymers, and hydrogels, have been elaborated with state-of-the-art bioengineering strategies for minimally invasive, continuous, and multiplexed sensing. Microneedle sensors have been employed to detect a wide range of biomarkers from electrolytes, metabolites, polysaccharides, nucleic acids, proteins to drugs. Insightful perspectives are outlined from biofluid, microneedles, biosensors, POC devices, and theragnostic instruments, which depict a bright future of the upcoming personalized and intelligent health management.