Abstract: Antibody-drug conjugates (ADCs) have emerged as a research hotspot in the development of antitumor agents due to their strong efficacy and specificity. However, the safe therapeutic window of ADCs has been restricted by such factors as off-tumor target binding and non-specific uptake of ADCs, which has led to the termination of numerous ADC research projects at the clinical trial stage. Focusing on antitumor therapy, this article elaborates on the influence of antibody components on the therapeutic window of ADCs, and highlights the current antibody engineering modification strategies for broadening the therapeutic window of ADCs, aiming to provide some reference for the development of the next generation of ADCs with low toxicity and high specificity.