The antibiotic resistome harbored in various sources across a large geographical scale can be characterized based on antibiotic-resistant bacteria (ARBs) and genes (ARGs) along with mobile genetic elements (MGEs). Several factors in wastewater treatment plants (WWTPs) contribute to the breeding of resistant genes in wastewater microbiomes. The effect of potential selective pressures such as metals, disinfectants, pesticides, and other organic pollutants is supposedly determining the fate of ARB and ARGs. Mechanistically, integrons and MGEs are suggested as one of the important media for resistance-gene transfer. A new set of molecular techniques, such as quantitative polymerase chain reaction (qPCR) analyses, gene-specific PCR, and computational approaches like metagenomics are developed in order to understand the complex microbial system of wastewater treatment for elucidation of the composition, quantification, and distribution of different bacterial groups. The environmental footprint of the antibiotic contamination-mediated emergence and dissemination of ARB and ARGs from the treatment plant into the downstream aquatic and soil ecosystems was recently emphasized. This chapter aims to discuss the ecology of ARB and ARGs in the treatment plant and distribution patterns and resistance determinants in various downstream habitats. Application of these advanced methods in the photochemical water treatment for disinfecting resistant microbial species is discussed.