Thermoplastic materials like High Density Polyethylene (HDPE) and Polytetrafluoroethylene (PTFE) are promising candidates for specialty industry/aerospace sectors considering their exceptional properties and lower densities. However, the low surface energy leading to poor wetting and reduced adhesion curtails the scope of their wide-spread usage. In this work, we report adhesion promoter primers based on epoxy.catechol with and without fluorinated polymer and investigated their adhesion promotion efficiency on low/high surface energy substrates. The rational design of catechol-fluorine-epoxy hybrid network, mimicking mussel chemistry enabled a non-destructive surface activating approach resulting in profound adhesion promotion. The fluorine containing primer could effectively enhance adhesion between homo and hetero interfaces of Aluminium/HDPE/PTFE owing to the good interface interaction and could outperform common etching methods. A series of molecular level characterizations together with computational and AFM studies provided evidences for the high degree of interaction of the primer between the substrates and epoxy-based adhesives. Bond integrity endurance test using a weight of 10 and 20 kg resulted in ‘no fail’ categorization for the primed substrates during the entire 40 days test duration. The catechol-functionalized primers reported here can be a good overreaching approach to keep non-polar substrates afloat in advanced sectors.