Environmental chemistry and biological sciences must work closely together to fully comprehend ecotoxicological impacts. Bioaccumulation lipophilicity is a criterion for the environmental persistence of OMCs. A M–C bond within organometallics might get broken or reformed under ecological conditions. OMC biological activity and environmental risk have gained significant attention. It discusses how temperature, salinity, and pH affect the chemical behavior of OMCs (pH-dependent dual Langmuir model). Pollutant absorption and bioavailability cannot be considered separate chemical or biological issues. This chapter focuses on speciation mechanisms of organometal (loid)s, competitive adsorption-desorption of BTs, and diffusion. Models to calculate TBT release from sediment are displayed. Ecotoxicological aspects of OMCs are deeply discussed with special reference to ecological risk assessment (RQ = PEC/PNEC) to create early warning systems. Influence of environmental factors (pH, salinity) and minerals, organic carbons, and quartz on the ecotoxicity of OMCs are addressed. Organometallic species react with proteins, and the decay of the myelin coating on nerve fibers is a two mode of action for OMC toxicity. Ca2+-dependent and Mg-ATPase activity are two mechanisms highlighting the toxicity of organotin compounds. Human health risk via tolerable average residue level (TARL), toxic unit (TU), cancer risk (CR), risk quotient (RQ), screening level (SL), target hazard quotient (THQ), and probabilistic distribution (Intakei,k (x, y)) are evaluated. The biosensing potential of OMCs in aquatic systems is assessed, and two examples of biomarkers of TBT in marine invertebrates (molecular genetic and imposex) are discussed. An overview highlighting the cutoff points of the ecological evaluation technique for OMCs is presented.