Nanocarriers have been developed to overcome the limitations of conventional therapeutics by enabling site-specific drug delivery. However, to reach diseased sites, nanocarriers must overcome sequential biological barriers, each demanding specific shapes for efficient traversal. Thus, relying on a simple shape proves challenging in traversing all biological barriers for the successful accumulation of nanocarriers at diseased sites. Here, to integrate the benefits of different simple shapes, nanocarriers adopt a coupled shape featuring heterogeneous curvatures within a single vesicle, where distinct curvatures are customized for specific biological barriers. This research holds the potential to significantly advance the development of next-generation nanocarriers.