These findings established a new paradigm for designing water-compatible NIR nanoprobes by fully leveraging the NIR-I biological window. The WINPs’ exceptional stability, high QY, and low-power operation address long-standing challenges in aqueous biosensing. Looking forward, several avenues remain open for further development: (1) expanding the application modes of the WINP system by leveraging its distinct lifetime signatures and environmentally sensitive spectral shifts; (2) exploiting the intrinsic NIR-II emission of Nd³⁺ (e.g., ~1060 nm and ~1330 nm transitions) to develop probes with deeper tissue penetration for in vivo sensing and imaging; and (3) surface-engineering for broader biomarker conjugation. With their low excitation power requirements and compatibility with silicon detectors, WINPs are poised to advance point-of-care testing and deep-tissue imaging, bridging the gap between laboratory innovation and real-world biomedical applications.