Microplastics (MPs) are synthetic polymers which have potentially emerged as one of the persistent, mobile pollutants in both terrestrial and aquatic environments. The polymer specific physicochemical properties, ageing, surface functional groups and hydrogen bonded structure lead to strong interactions and affinity towards a wide range of emerging pollutants co-existing the ecosystem. This review primarily focuses on the recent advances in understanding microplastic and emerging pollutant-based interactions at the molecular level, highlighting hydrophobic partitioning, electrostatic interactions, π–π stacking, and water-mediated hydrogen bonding. Here we light the contribution of the said mechanism in the generation of MPs-emerging pollutant associated complex pollutants and also illustrates the efficiency, scalability, environmental sustainability, and potential limitations of various removal methods. The complex pollutants comprise microplastics and other co-contaminants adsorbed onto the surface of the microplastics. These complex pollutants possess enhanced ecotoxicological implications, enhanced bioavailability as well as remedial challenges. Furthermore, it also focusses on the identification of key mechanistic research gaps and helps articulate research design principles for liquid-phase remediation strategies. Thus, the integration of the interaction dynamics, removal methodologies, and related challenges could provide potential mitigation measures to address the challenges imposed by microplastics and their co-contaminants in the environment.