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Antibody–drug conjugates (ADCs) are the gold standard for targeted drug delivery systems, but their chemical design imposes constraints that, if addressed, could enable a new generation of cancer therapeutics and imaging modalities. For example, due to bioconjugation limitations, the payload scope of ADCs is restricted to highly potent payloads with inherently unselective mechanisms of action, leading to narrow therapeutic windows and resistance. This seminar will introduce a new platform called Antibody–Bottlebrush prodrug Conjugates (ABCs) that can potentially address these challenges. ABCs feature a modular design that allows drug-to-antibody ratios (DARs) from ~1–135 while maintaining strong target binding, efficient cellular uptake, and favorable pharmacokinetics and biodistribution. Leveraging their capability to access very high DARs, ABCs can carry payloads (e.g., 10-fold less potent than existing ADC payloads) that are insufficiently potent to be used in traditional ADCs, thereby enabling new mechanisms-of-action. Moreover, ABCs are readily amenable to using various payload combinations, release mechanisms, and non-drug (e.g., imaging) agents. ABCs display efficacies on par with or superior to clinical ADCs in preclinical tumor models at clinically relevant payload doses, motivating their further clinical translation.