Herein, we developed a fully polymerizable, peptide-targeted, camptothecin polymeric prodrug system. Two prodrug monomers were synthesized via esterification of camptothecin (20Cam) and 10-hydroxycamptothecin (10Cam) with mono-2-(methacryloyloxy)ethyl succinate (SMA) resulting in polymerizable forms of the aliphatic ester- and aromatic ester-linked drugs respectively. These monomers were then incorporated into zwitterionic polymers via RAFT copolymerization of the prodrug monomers with a tert-butyl ester protected carboxy betaine monomer. Subsequent deprotection of the tert-butyl residues with TFA yielded carboxy betaine methacrylate (CBM) scaffolds with controlled prodrug incorporation. Reverse phase HPLC was then employed to establish drug release kinetics in human serum at 37 °C for the resultant polymeric prodrugs. Copolymers containing 10Cam residues linked via aromatic esters showed faster hydrolysis rates with 59% drug released at 7 days, while copolymers with 20Cam residues linked via aliphatic esters showed only 28% drug release over the same time period. These differences in drug release kinetics were then shown to correlate with large differences in cytotoxic activity in SKOV3 ovarian cancer cell cultures. At 72 hours, the IC50s of aromatic- and aliphatic-ester linked prodrugs were 56 nM and 4776 nM, respectively. An EGFR-targeting peptide sequence, GE11, was then directly incorporated into the polymeric prodrugs via RAFT copolymerization of the polymeric prodrugs with a peptide macronomer. The GE11-targeted polymeric prodrugs showed enhanced targeting and cytotoxic activity in SKOV3 cell cultures relative to untargeted polymers containing the negative control sequence HW12. Following pulse-chase treatment (15 min, 37 °C), the 72 hours IC50 of GE11 targeted prodrug was determined to be 1597 nM, in contrast to 3399 nM for the non-targeted control.