Controlled assembly of nanoparticles into asymmetric configurations is of great interest due to their novel properties and promising applications. In this Article, we report a generic strategy for the synthesis of dimer nanoclusters and asymmetric nanoassemblies by using magnetic colloidal substrates, on which tailored surface modification and controlled physical confinement are applied. The modularity of our approach facilitates the fabrication of asymmetric nanostructures with varying sizes, shapes, compositions, surface chemistry, and surface hydrophobicity. Success in the syntheses sheds a light on the versatility of our strategy in rationally designing and synthesizing asymmetric nanostructures with tailored properties and functionalities.