Improving the efficiency, cell survival, and throughput of methods to modify and control the genetic expression of cells is of great benefit to biology and medicine. We investigate, both computationally and experimentally, a nanostructured substrate made of tipless pyramids for plasmonic-induced transfection. By optimizing the geometrical parameters for an excitation wavelength of 800 nm, we demonstrate a 100-fold intensity enhancement of the electric near field at the cell–substrate contact area, while the low absorption typical for gold is maintained. We demonstrate that such a substrate can induce transient poration of cells by a purely optically induced process.