This review explores the integration of aptamers and stimuli-responsive platforms in targeted drug delivery systems for enhanced anticancer therapy. Aptamers, short nucleic acid sequences with high specificity and affinity, are used as targeting moieties to deliver drugs to cancer cells. The review discusses the versatile applications of aptamers conjugated with gold, silica, and carbon materials, emphasizing their potential in achieving precise and targeted drug delivery. Additionally, the review examines stimuli-responsive drug-delivery systems, focusing on spatial anticancer therapy. Tumor microenvironment-responsive nanoparticles are detailed, highlighting their ability to exploit dynamic conditions within cancerous tissues for controlled drug release. External stimuli-responsive strategies, including ultrasound-mediated, photo-responsive, and magnetic-guided drug-delivery systems, are also explored for their role in achieving synergistic anticancer effects. The review integrates diverse approaches to precision medicine, showcasing the potential of aptamers and stimuli-responsive systems to revolutionize drug-delivery strategies for enhanced anticancer therapy.This review explores the integration of aptamers and stimuli-responsive platforms in targeted drug delivery systems for enhanced anticancer therapy. Aptamers, short nucleic acid sequences with high specificity and affinity, are used as targeting moieties to deliver drugs to cancer cells. The review discusses the versatile applications of aptamers conjugated with gold, silica, and carbon materials, emphasizing their potential in achieving precise and targeted drug delivery. Additionally, the review examines stimuli-responsive drug-delivery systems, focusing on spatial anticancer therapy. Tumor microenvironment-responsive nanoparticles are detailed, highlighting their ability to exploit dynamic conditions within cancerous tissues for controlled drug release. External stimuli-responsive strategies, including ultrasound-mediated, photo-responsive, and magnetic-guided drug-delivery systems, are also explored for their role in achieving synergistic anticancer effects. The review integrates diverse approaches to precision medicine, showcasing the potential of aptamers and stimuli-responsive systems to revolutionize drug-delivery strategies for enhanced anticancer therapy.