This chapter explores the complex influences of heavy metals (HMs), microorganisms, and other radioactive elements on uranium solubility in aqueous environments. The presence of HMs such as lead (Pb), cadmium (Cd), and arsenic (As) can significantly alter uranium speciation and solubility through competitive adsorption, complexation, and co-precipitation processes. The role of microorganisms is examined, with a focus on microbial oxidation and reduction of uranium, biofilm formation, and the impact of microbial metabolites on uranium mobility. This chapter also addresses the synergistic and antagonistic interactions between uranium and other radioactive elements, such as thorium and radium, in natural and contaminated water systems. In addition, integrated case studies provide useful insights into the multifaceted interactions in real-world scenarios, highlighting the challenges in predicting uranium behavior in the presence of multiple contaminants. Advanced analytical techniques, including spectroscopic and microscopic methods, are discussed for their utility in elucidating these interactions. The combined health and environmental risks posed by complex contaminant mixtures are assessed, with an emphasis on developing robust risk assessment frameworks. Future research directions are proposed to address the emerging challenges in understanding and managing uranium solubility in the context of multi-contaminant environments.