DNA nanostructures, such as DNA origami, tetrahedral, nanoflower, cruciform, nanostar, nanocentipede, and nanococklebur, are versatile platforms for drug delivery due to their ability to traverse cell membranes and deliver cargo to the nucleus. Aptamers, formed in vitro, are particularly useful for targeted delivery due to their high selectivity and low immunogenicity. This review highlights recent advancements in the formation and modification of aptamer-modified DNA nanostructures for drug delivery systems. DNA nanostructures exhibit structural and functional versatility, with B-DNA serving as a double-stranded helix that can self-assemble into complex architectures. DNA nanotechnology's predictable and programmable interactions, along with its stability and malleability, make it a valuable tool for creating intricate nanostructures. These structures can be functionalized and loaded with various biomolecules, including drugs, targeting ligands, and aptamers, enhancing their efficiency in drug delivery. The review also discusses the stability and biocompatibility of DNA nanostructures under biological conditions, emphasizing the importance of pH control and the presence of Mg2+ ions. Additionally, it explores the use of DNA nanostructures for targeted drug delivery, particularly in cancer therapy, and the role of aptamers in improving cellular uptake and therapeutic efficacy. The integration of aptamers into DNA nanostructures, such as DNA origami and tetrahedral structures, has shown significant promise in enhancing the delivery of drugs and therapeutic agents to specific targets, demonstrating the potential of DNA nanotechnology in precision medicine.DNA nanostructures, such as DNA origami, tetrahedral, nanoflower, cruciform, nanostar, nanocentipede, and nanococklebur, are versatile platforms for drug delivery due to their ability to traverse cell membranes and deliver cargo to the nucleus. Aptamers, formed in vitro, are particularly useful for targeted delivery due to their high selectivity and low immunogenicity. This review highlights recent advancements in the formation and modification of aptamer-modified DNA nanostructures for drug delivery systems. DNA nanostructures exhibit structural and functional versatility, with B-DNA serving as a double-stranded helix that can self-assemble into complex architectures. DNA nanotechnology's predictable and programmable interactions, along with its stability and malleability, make it a valuable tool for creating intricate nanostructures. These structures can be functionalized and loaded with various biomolecules, including drugs, targeting ligands, and aptamers, enhancing their efficiency in drug delivery. The review also discusses the stability and biocompatibility of DNA nanostructures under biological conditions, emphasizing the importance of pH control and the presence of Mg2+ ions. Additionally, it explores the use of DNA nanostructures for targeted drug delivery, particularly in cancer therapy, and the role of aptamers in improving cellular uptake and therapeutic efficacy. The integration of aptamers into DNA nanostructures, such as DNA origami and tetrahedral structures, has shown significant promise in enhancing the delivery of drugs and therapeutic agents to specific targets, demonstrating the potential of DNA nanotechnology in precision medicine.