Hetero-nanoparticles represent a new class of nanomaterials exhibiting intriguing multifunctional and collective properties which could find applications in photovoltaics, fuel-cell catalysis, medical imaging and therapy, and electronics. In this paper, we report a novel polymer-single-crystal-templating (PSCryT) approach for the controllable synthesis of hetero-nanoparticles. 2D polymer single crystals are used to direct self-assembly of nanoparticles, yielding bicomponent Fe₃O₄–Pt, Fe₃O₄–Au, SiO₂–Pt, and SiO₂–Au and tricomponent Fe₃O₄–Pt–Au hetero-nanoparticles with fine-tuned structures. The as-synthesized hetero-nanoparticles possess collective properties derived from the interface between different particles. For example, compared with pure Pt nanoparticles, Fe₃O₄–Pt showed enhanced catalytic activity when used in 4-nitrophenol reduction reaction. The PSCryT method is simple, versatile and can be performed in a rational, step-wise manner under mild synthesis conditions. It therefore provides a great opportunity for the development of designer hetero-nanoparticles targeted for various applications.