Manufacturing of nanoscale complex metal oxides (CMOs) is on the rise, concurrent with their use in mobile devices and renewable energy applications. A key example is the delafossite structure type, which has found increased use as one of the prominent families of intercalation materials used in lithium-ion batteries (LIBs). The delafossite CMOs used in LIBs are the electroactive components of the cathode, and the prototypical example is LiCoO 2 (LCO). To decrease the cost and increase the performance of materials based on LCO, compositional tuning has led to Li(Ni 1/3 Mn 1/3 Co 1/3 )O 2 (NMC) materials, and other variants such as high-Ni NMC compositions, which are readily synthesizable and demonstrate both high voltage in operation and enhanced cycle stability. While compositionally tuned variants of LCO and NMC have been advantageous because of their improved properties and ease of manufacturing, they also contain transition metals whose release has been shown to be potentially toxic to a wide variety of organisms. The proposed mechanisms of negative biological impact include both a) an increased concentration of potentially toxic cations in solution via incongruent CMO surface release of Ni and Co 14 and b) oxidative stress caused by the generation of reactive oxygen species (ROS) in situ. To better understand the thermodynamics of surface transformations that enable cation release, we evoke a DFT+ solvent ion model. Our test cases included compositionally tuned variants of NMC (equistoichiometric and Mn-rich NMC) that contain multiple cations whose oxidation states depended upon atomistic composition, surface termination, and the formation of vacancies. We were able to combine DFT-computed (001) surface vacancy energies and experimentally determined aqueous thermodynamics to show that metal release depends upon oxidation state and chemical environment of the cations, via surface terminations and neighboring cations. More importantly we were able to agree with trends in experimental release (Li > Ni > Co > Mn) and go on to inform experiments using Ni-rich NMC compositions (Buchman et al., under review).