Facile, durable and biocompatible integration of hybrid Lab-on-a-Chip devices has remained an important challenge in microengineering. Here, the robust and seamless integration of off-stoichiometry thiol-ene-epoxy (OSTE+) thermosets with a diverse range of thermoplastic and glass materials is demonstrated. While direct bonding offers sturdy proprieties for the majority of the material hybrids (up to 1.5 MPa), further surface priming enhances the bonding strength for those of lower surface energy (up to seven-fold). Using microfluidic devices with a unique configuration of chambers and microchannels down to 100 µm, the impact of various bonding methods on their fluidic functionality is further shown. To investigate the utility of hybrid devices for pharmacological and toxicological studies, both pristine and primed devices are benchmarked against polydimethylsiloxane (PDMS) with regard to cell biocompatibility and drug absorption. While being on par with PDMS in terms of cell viability, pristine OSTE+ devices show an 11-fold lower absorption of hydrophobic drug molecules. Although surface priming enhances the bonding strength, it compromises other criteria in device performance and biological applications. Combined, results demonstrate a novel integration approach for facile manufacturing of hybrid microfluidic devices using a material toolbox suitable for cell and pharmaceutical studies.