AbstractNucleic acid‐based therapies have changed the paradigm of cancer treatment, where conventional treatment modalities still have several limitations in terms of efficacy and severe side effects. However, these biomolecules have a short half‐life in vivo, requiring multiple administrations, resulting in severe suffering, discomfort, and poor patient compliance. In the early days of (nano)biotechnology, these problems caused concern in the medical community, but recently it has been recognized that these challenges can be overcome by developing innovative formulations. This review focuses on the use of vinyl polymer‐based materials for the protection and delivery of nucleic acids in cancer. First, an overview of the properties of nucleic acids and their versatility as drugs is provided. Then, key information on the achievements to date, the most effective delivery methods, and the evaluation of functionalization approaches (stimulatory strategies) are critically discussed to highlight the importance of vinyl polymers in the new cancer treatment approaches.This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures