Carbon-fibre-reinforced-polyetherketonketone (CF/PEKK) has attracted increasing interest in the aviation industry due to its self-healing/recycling properties. However, its machining performance is not well understood and there is a lack of optimization study for minimizing its hole damage and improving the production efficiency. Here, we report the first multi-objective optimization study for CF/PEKK drilling. A hybrid optimization algorithm integrating NSGA-II and TOPSIS is deployed to obtain the Pareto solutions and rank the multiple solutions based on closeness to ideal solutions. To highlight the impact of different matrix properties on the optimization outcome, comparative study with conventional thermoset CF/epoxy was carried out for the first time. Experimental validation shows the proposed method can achieve 91.5-95.7% prediction accuracy and the Pareto solutions effectively controlled the delamination and thermal damage within permissible tolerance. The vastly different optimal drilling parameters identified for CF/PEKK and CF/epoxy is attributed to the thermoplastic nature of CF/PEKK with unique thermal/mechanical interaction characteristics.