Electroporation is a widely used physical technique that employs pulsed electric fields to temporarily permeabilize cell membranes, enabling the efficient delivery of therapeutic molecules such as drugs and genes. Alongside this, cold atmospheric plasma (CAP) has emerged as a promising alternative, offering a multifaceted mechanism of action. CAP generates a mix of reactive oxygen and nitrogen species, UV photons, and transient electric fields, which together induce membrane permeabilization through lipid peroxidation, electroporation-like pore formation, and activation of endocytic pathways. Unlike traditional electroporation, CAP can operate without direct electrode contact and at atmospheric conditions, making it suitable for sensitive biological applications. This review explores the underlying biophysical mechanisms of both electroporation and plasma-induced permeabilization, compares different device configurations, and examines their applications in drug and gene delivery systems. It also discusses the relative benefits, limitations, and safety considerations, and outlines key research directions needed to optimize these technologies for clinical translation. Keywords: Electroporation, Cold Atmospheric Plasma (CAP), Cell Membrane Permeabilization, Gene Delivery, Drug Delivery, Reactive Oxygen and Nitrogen Species (RONS)