A simple method for the encapsulation of quantum dots (QDs) in virus-like particle (VLP) nanoassemblies with tuneable structural properties and enhanced biocompatibility is presented. Cowpea chlorotic mottle virus-based capsid proteins assemble around the carboxylated QDs to form QD/VLP nanoassemblies of different capsid size as a function of pH and ionic strength. Detailed structural characterizations verify that nanoassemblies with probably native capsid icosahedral symmetry (T = 3) are obtained at low pH and high ionic strength (pH 5.0, 1.0 M NaCl), whereas high pH and low ionic strength conditions (pH 7.5, 0.3 M NaCl) result in the formation of smaller assembly sizes similar to T = 1 symmetry. In vitro studies reveal that QD/VLP nanoassemblies are efficiently internalized by RAW 264.7 macrophages and HeLa cells with no signs of toxicity at QD concentrations exceeding the potentially-toxic levels. The presented route holds great promise for preparation of size-tuneable, robust, non-toxic luminescent probes for long term cellular imaging applications. Furthermore, thanks to the possibility of chemical and genetic manipulation of the viral protein shell encaging the QDs, the nanoassemblies have potential for in vivo targeting applications.