We have systematically investigated the effect of physicochemical conditions, such as pH, salt concentration, and DNA/nanoparticle ratio, on the chemical conjugation process and structural and optical stability of carboxyl-functionalized quantum dots (QDs) functionalized with amino-modified DNA. We reveal the relationship between aqueous conditions and the amount of DNA conjugated on QDs, colloidal stability, and yield of the final QD-DNA conjugates. By carefully adjusting the environmental variables we have successfully achieved up to 20 DNA strands conjugated per QD, and demonstrated how this number can be tuned. The fabricated QD-DNA,conjugates are dispersed and optically stable in salted solutions for over a month. We have also evaluated the involved interparticle interactions to explain the solution behavior of QD-DNA conjugates. Our, results provide a basic understanding of the physiochemical processes governing a nanoparticle-biomolecule conjugation and the structural stability of the formed conjugates. Such fabricated QD-DNA conjugates, might be of great benefit for programmable assemblies of optically active nanomaterials and for emerging biosensing methods based on nanomaterials.