SN38 is an active metabolite of irinotecan, which was approved for clinical use in metastatic colorectal cancers. However, poor aqueous solubility and inactivation at pH below 6 are the main limitations of its use. In the current study, we separately conjugated α-, β- and γ-cyclodextrins to graphene oxide sheets to produce stable, biocompatible nanocarriers for SN38 delivery. The conjugates were coordinated with Fe₃O₄ in the form of superparamagnetic iron oxide nanoparticles. Then, SN38 was non-covalently conjugated to the developed nano-conjugate in order to overcome its solubility and stability problems and reduce its side effects. The loading efficiency of different formulations was between 13–22%. α-CD-GO-Fe₃O₄-SN38 and γ-CD-GO-Fe₃O₄-SN38 significantly enhanced the cytotoxicity of the conjugates compared to the free drug. Besides, combined photothermal/chemotherapy study revealed that all the designed nano-platforms reduced the HT-29 cell line viability synergistically in vitro. However, β-CD-GO-Fe₃O₄-SN38 showed the highest synergistic effect compared to other formulations. In conclusion, the results of the study revealed that such combined treatment platforms might find their way as potential therapeutics to fight against cancer.