<p>Microplastics are widely recognized as persistent and pervasive contaminants that endanger human health and ecosystems. Traditional remedial techniques are problematic due to high costs and inefficiency. One sustainable method of dissolving tough polymers into recyclable parts is through microbial and enzymatic engineering. Recent advances in genome-editing technologies, enzyme redesign, and synthetic biology particularly CRISPR-based systems have transformed the way we approach enhancing the efficiency of biodegradation. Recent CRISPR applications, such as base editing and promoter modification, have improved the stability and expression of enzymes, accelerating the catalytic activity of PET hydrolases, including PETase and cutinase. To enable scalable plastic biodegradation, this review combines hybrid CRISPR-based systems with microbial and enzyme engineering techniques. The goals of computational and machine learning–based enzyme design is thermostability and substrate adaptation, while hybrid microbial communities made up of modified bacteria and fungi improve degradation through cooperative processes. Furthermore, combining synthetic biology with hybrid remediation techniques, such as biofilm reactors and enzyme-nanoparticle conjugates, links laboratory research developments with real-world applications. However, issues remain regarding the scalability of polyethylene (PE) and polystyrene (PS) degradation, biosafety standards for genetically modified organisms (GMOs), and environmental hazards associated with degradation byproducts. To effectively manage plastic waste, future research should focus on creating thermostable enzymes, forming synthetic consortia guided by multi-omics, and developing safe hybrid bio-physical systems that support circular bio economy models.</p>