A strategy for the preparation of bimetallic mesoflowers (MFs) has been demonstrated by a simple overgrowth reaction. We make hybrid MFs containing Au core and shells of different metals, such as Ag and Pt, by tuning the experimental conditions so as to study region-specific overgrowth. This selective growth is attributed to the specific binding affinity of cetyltrimethylammonium bromide (CTAB) at different crystal planes of Au MF surfaces. We also studied the region-specific, composition dependent surface-enhanced Raman scattering (SERS) activity of single bimetallic MFs to understand, their chemical environment. Substrate effects on the SERS activity at single particle level were evaluated by a comparative study of the Raman images of Au, Au/Ag, and Au/Pt MFs. Region-specific SERS activity exhibited by single Au/Ag MF provides an insight into the SERS activity of bimetallic MFs over their monometallic analogues. © 2010 American Chemical Society.