Aptamers (Aps) are short single-strand nucleic acids exhibiting unique 3D structure which facilitate their targeting potential against various cancer molecular markers (CMMs). Such features of Aps not only make them as suitable homing agents in targeted drug delivery systems (DDSs) but also candidate them as macromolecules that inhibit the interaction of the target ligand with other proteins. On the other hand, the conjugation of Aps with another therapeutic molecule such as antisense oligonucleotides (ASOs), siRNAs/miRNAs, Aps, toxins, chemotherapeutic agents, DNAzymes/Ribozymes provides hopeful strategy to eradicate the malignancies and overcome the off-target unwanted side effects. Such prominent features of Aps make them a promising TREATMENT modality to overcome the tumor complexity and heterogeneity, which can be consequently applied for PERSONALIZED therapy of cancer by using bispecific Ap-based therapeutics.