This study presents a long-lived NIR-IIb luminogenic nanoagent (ErPc-Sa NPs) based on a newly designed erbium phthalocyaninate complex with impressive quantum yield at 1530 nm (Er, 2.81%) via single molecular self-assembly; NIR-IIb (1500-1700 nm) imaging holds tremendous potential for targeted screening of deep-seated pathological changes in tissues, though developing activatable NIR-IIb probes has been challenging. The luminescence of the nanoagent is switched on at 1530 nm upon activation by carbonic anhydrase (CA), a hypoxic tumor marker, under 680 nm excitation. ErPc-Sa NPs shows high specificity toward CA on MDA-MB-231 cell membranes under hypoxic conditions and the localized CA in tumor-bearing mice with NIR-IIb imaging.