<p>Nanotechnology-based drug delivery systems have improved target medicines’ therapeutic efficacy and specificity in cancer therapy. Imatinib, one of the tyrosine kinase inhibitors widely used for treating chronic myeloid leukemia and gastrointestinal stromal tumors (GIST), faces many drawbacks, such as poor solubility, reduced bioavailability, and the development of resistance. The paper critically reviews advances in nanotechnology-based approaches toward the delivery of Imatinib, relating to polymeric, lipid-based, carbon-based, and stimuli-responsive nanoparticles. These methods enhance solubility, stability, and targeted distribution and are often used to facilitate the co-delivery of other anticancer drugs with considerable problems in cancer treatment. Although much potential for these technologies exists, scalability, safety, and regulatory approval, among other features, need resolution before real cost can meet clinical efficacy. Further directions would go toward bio-inspired system development, enhancing regulatory frameworks, and cost-effective manufacturing processes that bring nanotechnology into the realm of standard treatment for cancer.</p> Graphical Abstract <p></p>