An innovative and versatile microextraction technique based on nanoconfined solvent on carbon nanofibers has been conceived, realized, optimized, and presented here. The extraction capabilities of this technique toward polar, medium polar, and/or nonpolar substances can be easily modulated based on the nanoconfined solvent used. The so-called nanoconfined liquid phase nanoextraction showed excellent characteristics in terms of extraction recoveries, extraction time (≤1 min), reliability, and versatility. A needle-tip device has been realized on the base of this extraction process to allow direct extraction procedures and minimally invasive testing: this device guarantees a safe insertion in aqueous or soft samples, and it allows a fast and minimally invasive analyte extraction. Due to its versatility, chemical stability, and mechanical flexibility, nanoconfined liquid phase nanoextraction can be considered a powerful candidate for high-throughput analyses of biological samples.