This work focuses on the synthesis and self-assembly of triphilic poly(2-oxazoline) triblock copolymers with high fluorine content toward our future aim of developing poly(2-oxazoline) magnetic resonance imaging (MRI) contrast agents. A highly fluorinated 2-substituted-2-oxazoline monomer, namely 2-(1H,1H,2H,2H-perfluorooctyl)-2-oxazoline, was synthesized using the Grignard reaction. The polymerization kinetics of the synthesized monomer was studied, and it was used for the preparation of triblock copolymers with hydrophilic 2-methyl-2-oxazoline, hydrophobic 2-octyl-2-oxazoline, and fluorophilic blocks by cationic ring-opening polymerization yielding polymers with low relatively dispersity (1.21.4). The presence of the blocks with the different nature in one copolymer structure facilitated self-assembly of the copolymers in water and dimethyl sulfoxide as observed by dynamic light scattering, cryo-transmission electron microscopy, and small-angle neutron scattering. The nanoparticle morphology is strongly influenced by the order and length of each block and the nature of solvent, leading to nanoparticles with coreshell structure as confirmed by small-angle neutron scattering. The reported poly(2-oxazoline) block copolymers with high fluorine content have high potential for future development of MRI contrast agents.