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The pursuit of compact and integrated devices has stimulated a growing demand for multifunctional sensors with rapid and accurate responses to various physical parameters, either separately or simultaneously. Fluorescent fiber sensors have the advantages of robust stability, light weight, and compact geometry, enabling real-time and noninvasive signal detection by monitoring the fluorescence parameters. Despite substantial progress in fluorescence sensors, achieving multifunctional sensing in a single optical fiber remains challenging. To solve this problem, in this study, we present a bottom-up strategy to design and fabricate thermally drawn multifunctional fiber sensors by incorporating functional nanocrystals with temperature and pressure fluorescence responses into a transparent glass matrix. To generate the desired nanocrystal-in-glass composite (NGC) fiber, the fluorescent activators, incorporated nanocrystals, glassy core materials, and cladding matrix are rationally designed. Utilizing the fluorescence intensity ratio technique, a self-calibrated fiber sensor is demonstrated, with a bi-functional response to temperature and pressure. For temperature sensing, the NGC fiber exhibits temperature-dependent near-infrared emission at temperatures up to 573 K with a maximum absolute sensitivity of 0.019 K -1 . A pressure-dependent upconversion emission is also realized in the visible spectral region, with a linear slope of -0.065. The successful demonstration of multifunctional NGC fiber sensors provides an efficient pathway for new paradigms of multifunctional sensors as well as a versatile strategy for future hybrid fibers with novel combinations of magnetic, optical, and mechanical properties., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2022 The Authors.)