In summary, the work by Liu et al. represents a huge breakthrough in the development of nonlinear luminescent nanomaterials, as it pushes forward the optical N to an unprecedented level of >500. It establishes a scalable paradigm for designing ultra-responsive optical materials through lattice engineering based on PA UC of lanthanide-doped NPs. Beyond enabling super-resolution imaging with great precision and accuracy, the extreme N may unlock potentials in ultrasensitive sensing, on-chip photonics, and quantum optics. Future efforts to miniaturize high-N NPs while addressing spatial heterogeneity will propel integrated quantum nanotechnologies, which relies on full understanding of the structure−property relationship of PA NPs.