This chapter explores the in-depth chemical process of the complex primordial radionuclide uranium (U), which is correlated with its solubility and the impact of interfering agents. The chemistry of uranium depends on the oxidation state, predominantly uranium (+4 and +6), which monitors the behavior of uranium in the environment. Uranium solubility poses potential health risks when it is transported into the environment and contaminated. The U (+6) oxidation state is soluble and leaches into natural sources, such as groundwater, soil, sediment and the food chain, by posing risks to drinking water and plantations, causing toxic effects on wildlife and humans. Organic compounds such as humic, citric and fulvic acids, in addition to synthetic organic pollutants and other ligands, increase uranium solubility and mobility in natural sources. Analogously, inorganic compounds such as carbonate, bicarbonate, chloride, sulfates, and iron and manganese oxides contribute to the mobility and solubility of uranium. Environmental factors, including microbial activities, redox conditions, and physicochemical parameters (pH, salinity, temperature and electrical conductivity), influence interfering agent interactions with the chemistry of uranium. By analyzing the complex interactions between the solubility of uranium and an interfering agent, this chapter reveals uranium chemistry and generates precautions for managing contamination in natural and industrial contexts.