Single-chain nanoparticles (SCNP) are a class of polymeric nanoparticles obtained from the intramolecular cross-linking of polymers bearing reactive pendant groups. The development of SCNP has drawn tremendous attention since the fabrication of SCNP mimics the self-folding behavior in natural biomacromolecules and is highly desirable for a variety of applications ranging from catalysis, nanomedicine, nanoreactors, and sensors. The versatility of novel chemistries available for SCNP synthesis has greatly expanded over the past decade. Significant progress was also made in the understanding of a structure-property relationship in the single-chain folding process. In this Viewpoint, we discuss the effect of precursor polymer topology on single polymer folding. We summarize the progress in SCNP of complex architectures and highlight unresolved issues in the field, such as scalability and topological purity of SCNP.