The facile fabrication of Gd-labeled superparamagnetic Fe₃O₄ nanoparticles (NPs) and fluorescent CuInS₂ (CIS) quantum dots conjugated with arginine-glycine-aspartic acid (RGD) peptides has been demonstrated, for tri-mode targeted T₁-, T₂-weighted magnetic resonance (MR) and fluorescence imaging of pancreatic cancer. The core–shell nanocomposites formed are water-dispersible, stable and biocompatible, as confirmed by MTT assay on BXPC-3 cells. Relaxivity measurements show a T₁ relaxivity (r₁) of 1.56 mM⁻¹ s⁻¹ and a T₂ relaxivity (r₂) of 23.22 mM⁻¹ s⁻¹, which enable T₁- and T₂-weighted MR imaging of cancer cells in vitro and in vivo. The MR imaging data clearly indicate that the multifunctional NPs can specifically target cancer cells with α_vβ₃ integrin over-expression on the cell surface, through a receptor-mediated delivery pathway. The T₁-weighted positive and T₂-weighted negative enhancement in the MR imaging significantly improves the diagnosis accuracy, and fluorescence imaging of tumor tissue can assist in clinical surgery. These findings suggest that these multifunctional NPs could be used as a platform for bimodal imaging (both MR and fluorescence) in various biological systems.