Single-chain polymer nanoparticles (SCNPs) obtained through chain collapse via intramolecular cross-linking are attracting significant interest for nanomedicine and biomimetic catalysis applications, among other fields. This interest arises from the possibility to bind active species (e.g., drugs and catalysts)-either temporally or permanently-to the SCNP local pockets formed upon chain collapse. However, direct quantification of the size and number of such local domains in solution-even if highly desirable-is currently highly demanding from an experimental point of view because of the small size involved (<5 nm). On the basis of a scaling analysis, we establish herein a connection between the global compaction degree (R/R 0) and the size (ξ) and number (n) of the "collapsed domains" generated upon SCNP formation at high dilution from a linear semiflexible precursor polymer. Results from molecular dynamics simulations and experimental data are used to validate this scaling analysis and to estimate the size and number of local domains in polystyrene SCNPs synthesized through a "click" chemistry procedure, as a representative system, as well as for relevant catalytic SCNPs containing Cu, Pt, and Ni atoms. Remarkably, the present work is a first step toward tuning the local domain size of the next generation of SCNPs for nanomedicine and bioinspired catalysis applications.