Since 2020, the concept of nucleic acid delivery has permeated households, thanks to the introduction of messenger RNA (mRNA) vaccines during the COVID-19 pandemic. Nucleic acid therapies, including vaccines, employ vectors to transport nucleic acid cargo, influencing gene expression or function. Naked DNAs and RNAs, as independent therapeutic agents, are charged and too large and fragile to traverse cellular membranes. They are also susceptible to degradation by nucleases in tissue and body fluids. Consequently, the design of gene therapy vectors plays a pivotal role in ensuring the safety and efficacy of the treatment. Viral vectors have proven effective for nucleic acid delivery because their evolutionary design relies on successful gene delivery. However, the clinical translation of viral vectors has been impeded by adverse immune responses, high production costs, off-target insertions, limited cargo gene size, and potential pathogenicity. Given these limitations of viral vectors, attention has pivoted towards non-viral vectors for nucleic acid delivery. Non-viral carriers are easier to produce, have better biocompatibility, and provide larger gene-carrying capacity than viral vectors. Further, non-viral vectors can be designed with a wide variety of chemistries, and this tunability enables unique functionalities at varied stages of the development and delivery process. For example, these vectors have taken the form of both organic vectors (i.e., liposome and polymer particles) and inorganic vectors (i.e., mesoporous silica, gold, carbon nanotubes, etc.). This variety of vectors provides access to stimuli-responsive release mechanisms (i.e. photo-and thermal-irradiation) and co-delivery of lysosomotropic reagents which improve nucleic acid release into the cytosol. Although non-viral vectors mark progress and improvements in design and desired properties for nucleic acid delivery vehicles, challenges remain.