Microdroplet array chips have great potential for biological applications. Both physical structure and chemical material modification are effective surface modification techniques for the generation of droplet arrays. However, single surface modification technique is constrained by either unstable infiltration state transition or the requirement for high surface tension. In this paper, we proposed a heterogeneous inner surface modification technique for an enclosed microdroplet array chip by coupling the physically structured surface modification that accelerates the wetting state of the aqueous solution, and the material-modified surface that can maintain this state, thus keeping the aqueous solution in a stable Wenzel state. This technique provides a stable surface energy difference for enhanced microdroplet array generation. We investigated the influences of variables that affect the heterogeneity of the inner surfaces of the chip, such as the contact angles of the upper and lower surfaces and the size of the micropores on the stability and size of the generated droplet. We also evaluated the compatibility of technique for different types of liquids and biological reagents for the droplet array generation. Furthermore, we demonstrated the potential of the droplet arrays generated in a heterogeneous dual-regulation manner for DNA amplification in loop-mediated isothermal amplification (LAMP).