The chemistry of ZnAl₂O₄ nanocrystal nucleation and growth is examined by X-ray scattering methods, and the results challenge the conventional understanding of its preparation by hydrothermal methods. The common assumption that a specific metal to hydroxide ion (M/OH) ratio is necessary to achieve a phase-pure product is shown to be inadequate. Pair distribution function analysis is used to identify distinct precursor structures, providing an understanding of why particular impurity phases are observed under certain M/OH ratios as heating is applied. In situ X-ray diffraction studies then probe the ZnAl₂O₄ growth in real time, from which optimal synthesis conditions and the influence of impurities is established. It is found that the heating rate plays a dominant role in impurity formation and dissolution. This observation is explored in three different hydrothermal synthesis methods (microwave, autoclave, and supercritical flow) having different intrinsic heating rates, and methodologies to prepare phase-pure ZnAl₂O₄ were successfully developed in each case. Ultimately, the atomic scale X-ray scattering information provides concrete guidance to tune the crystallite size, band gap, morphology, and defects of ZnAl₂O₄ nanocrystals in hydrothermal synthesis establishing a bottom up nonempirical approach to synthesis design.