There is a steady increase in plastic production in our day-to-day life. Without a real and efficient strategy for plastic waste management, it contributes to enormous environmental pollution. A promising strategy is to use enzymatic hydrolysis of plastics (e.g. PET) to depolymerise post-consumer waste and create a circular economy. To this end, several enzymes have been identified that show hydrolytic activity against PET, but none of the wild type sequences is suitable for industrial applications. PETase from Ideonella Sakaiensis shows moderate activity at low temperatures, offering a great scaffold that opens new possibilities for enzyme engineering. Based on its crystal structure, we have used computational modelling to design several PETase variants. We have iteratively combined mutations that improve the scaffold and use them as starting point for subsequent generations. Overall, we identified several variants with increased solubility, activity and thermal stability compared to the wild-type IsPETase. The structural characterization of the best-performing variants reveals new insights into their efficient catalytic activity and stability. Furthermore, we will discuss how these and future improvements of IsPETase could provide a potential solution for various sorts of PET waste treatment.