Antibody drug conjugates (ADCs) are specific tumor targeting complexes that are typically composed of monoclonal antibodies (mAbs) attached covalently to a cytotoxic payload via a chemical linker. The precision-based targeting ability of ADCs has revolutionized the world of cancer therapeutics. Currently, 13 ADCs have received FDA-approval, with the majority receiving breakthrough or accelerated approvals for various cancers. At present, an excess of 400 drug candidates are being investigated, tested, or are undergoing clinical trials worldwide. Designing an ‘ideal’ ADC presents unique challenges, as production and conjugation of the individual elements (antibody, linker, and payload) requires extremely high precision and control. Of the ADCs that have been approved as well as those under investigation, formulation is strictly guided to maintain effective antibody-antigen targeting and linker-payload compatibility with the goal of preserving stability in circulation; allowing specific release of the payload once it reaches it’s target and as such, upholding optimal therapeutic output. These complexities extend to antibody: structure and post-translational modifications, linker: location, size, length and hydrophobicity, and payload: cytotoxicity, immunogenicity and solubility. Herein, we review design and formulation strategies used in the approved ADCs since the first FDA-approved ADC through today, discussing biologic engineering modifications that have shown to improve clinical efficacy and the therapeutic index, while maintaining ADC stability.