In summary, the work by Zhang et al. establishes 1143 nm as a superior excitation wavelength for deep-tissue multiplexed imaging while providing a general strategy for engineering NIR-II luminescent Ln³⁺ nanoprobes via Ho³⁺ sensitization. The demonstrated six-channel NIR-II imaging system significantly advances capabilities for real-time monitoring of complex physiological interactions, offering transformative potential for preclinical research and diagnostic applications. Future integration with emerging detection technologies could further exploit the NC extended emission range, potentially enabling non-invasive monitoring of deep-tissue metabolic processes and multi-organ interactions with greatly improved resolution.