Cellular transfection is a method by which exogenous biomolecules can be introduced into the cells. In the fields of molecular and cellular biology, cellular transfection is considered an essential tool, specifically for applications such as drug delivery, cellular therapy, and biomedical imaging. Photoporation based cellular transfection approach uses high-intensity light energy to create membrane pores, sometimes nanoparticles are incorporated to achieve the result at low intensity. In this work, hybrid nanoparticles, composed of gold and polystyrene are used to mediate the photoporation. Laser fluence, exposure time, wavelength, the concentration of nanoparticles, and concentration of exogenous molecules are optimized for the successful delivery of propidium iodide dye, quantum dots, and plasmid into CL1-0, AGS, and P-19 cells. The best results (delivery efficiency of 92% and cell viability of 98%) are achieved in delivering propidium iodide dye into CL1-0 cells. © 2021 IEEE.