Nanomedicines have the potential to provide advanced therapeutic strategies in combating tumors. Polymer-prodrug-based nanomedicines are particularly attractive in cancer therapies owing to the maximum drug loading, prolonged blood circulation, and reduced premature leakage and side effects in comparison with conventional nanomaterials. However, the difficulty in precisely tuning the composition and drug loading of polymer-drug conjugates leads to batch-to-batch variations of the prodrugs, thus significantly restricting their clinical translation. Polyprodrug nanomedicines inherit the numerous intrinsic advantages of polymer-drug conjugates and exhibit well-controlled composition and drug loading via direct polymerization of therapeutic monomers, representing a promising nanomedicine for clinical tumor therapies. In this review, recent advances in the development of polyprodrug nanomedicines are summarized for tumor elimination. Various types of polyprodrug nanomedicines and the corresponding properties are first summarized. The unique advantages of polyprodrug nanomedicines and their key roles in various tumor therapies are further highlighted. Finally, current challenges and the perspectives on future research of polyprodrug nanomedicines are discussed.