Research was completed on the behaviour and fate of tetrabromobisphenol A (TBBPA) in pilot-scale membrane bioreactors and conventional activated sludge (CAS) process at the City of Guelph Wastewater Treatment Plant. Emphasis was on the physicochemical processes, biological transformation and sorption kinetics. Measurement of TBBPA at the environmental level can be challenging, so the main focus of this paper was the development of an analytical method for the nano-level determination of TBBPA. The approach used was gas chromatography-negative ion chemical ionization-mass spectrometry in select ion monitoring mode. For the wastewater matrix studied, the developed method had a low method detection level (MDL) of 2.4 ng/L. The matrix effects for influent and activated sludge mixed liquor were determined to be 36.5 ± 5.9% (n = 10) and 79.2 ± 4.5% (n = 10), respectively. Preliminary results show that the CAS system demonstrates better performance for TBBPA removal, with removal at 83%. This was corroborated by the batch experiments that showed that the synergistic effects of biodegradation and biosorption potentially provide more removal of the TBBPA through the activated sludge process.