Safe disposal of nuclear waste is essential to ensure sustainability of nuclear energy and environmental cleanup from nuclear activities. This is especially true for problematic radionuclides such as iodine, cesium, and strontium because of their half-life, volatility, and mobility in most disposal environments. An integrated approach by considering both radionuclide incorporation and release from host materials is essential to improve the performance of waste forms and develop new waste forms. Chemical bonding environment and properties of host material are intimately connected to how radionuclides get incorporated and how they get released to the environment. As an example, incorporation of iodine in apatite is investigated to understand crystal chemistry of iodoapatite using artificial neutral network simulation, which is effective to understand nonlinear relationship between chemical composition and properties of a crystal structure. The result suggests that there are a number of composition combinations of apatite, including Cs, Sr, Ba, Mo, V, and As apatites, that potentially incorporate iodine, greatly extending the compositional space for iodoapatite waste form. Future more, first-principles calculations suggest a number of predicted apatites are energetically stable, and a better route to synthesis is to increase synthesis temperature as the Gibbs free energy formation is calculated to decrease with temperature. The effect of beta decay on the stability such as 137Cs → 137Ba and 90Sr → 90Y → 90Zr can be mitigated by introducing appropriate electron acceptor at the neighboring sites in the structure. As demonstrated by first-principles calculations, the extra electron from beta decay is localized at a variable valence ion (ferric iron), which changes its oxidation state and becomes ferrous iron, with a significant stability improvement. Due to the nature of ionic bonding of iodine in a covalent bonded apatite lattice, the release of iodine from Pb10(VO4)6I2 apatite is observed to be incongruent. The iodine was initially released at a significantly higher rate than suggested by its stoichiometry with respect to lead and vanadium, gradually decreased over time, caused by an ion-exchange process that is faster than the dissolution rate of the Pb-V-O framework evidenced by the spectroscopic signature of OH groups in leached samples. These studies suggest that apatite-structured materials could be promising nuclear waste forms to incorporate these problematic radionuclides, and are capable to mitigate the beta decay induced instability, and have low iodine release rate in aqueous solutions.