Gefitinib (GEF) is an FDA-approved anti-cancer drug for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC). However, the efficacy of anticancer drugs is limited due to their non-specificity, lower accumulation at target sites, and systemic toxicity. Herein, we successfully synthesized a modified GEF (mGEF) drug and conjugated to Iron oxide nanoparticles (FeO NPs) for the treatment of NSCLC via magnetic resonance (MR) image-guided drug delivery. A traditional EDC coupling pathway uses mGEF to directly conjugate to FeO NPs to overcom the drug leakage issues. As a result, we found drug delivery on mGEF- FeO NPs exhibits excellent anticancer effects towards the PC9 cells selectively, with an estimated IC 50 value of 2.0 μM. Additionally, MRI and PET results demonstrate that the NPs could accumulate in tumor-specific regions with localized cell growth inhibition. Results also revealed that outer tumor region exhibiting a stronger contrast than the tinner tumor region which may due necrosis in inner tumor region. biodistribution further confirms FeO NPs are more biocompatible and are excreated after the treatment. Overall, we believe that this current strategy of drug modification combined with chemical conjugation on magnetic NPs will lead to improved cancer chemotherapy as well as understanding the tumor microenvironments for better therapeutic outcomes.