<p><i>Acinetobacter baumannii</i> as a critical priority gram-negative opportunistic pathogen has gained notoriety in recent decades, primarily due to its propensity to cause severe nosocomial infections. <i>Acinetobacter baumannii</i> is characterized by increased levels of resistance toward multiple classes of first-line and last-resort antibiotics, making it a serious threat to public health worldwide. Hybrid molecules, consist of two or more different pharmacophores, are able to modulate multiple targets simultaneously. Accordingly, hybrid molecules have the potential to overcome drug resistance, enhance the activity, improve pharmacokinetic properties and reduce the toxicity, and rational design of hybrid molecules is a promising strategy to provide potential prototypes for clinical deployment in the control and eradication of infections caused by drug-resistant <i>Acinetobacter baumannii</i>. The purpose of the present review article is to provide an emphasis on the current scenario (2020–present) of hybrid molecules with therapeutic potential against drug-resistant <i>Acinetobacter baumannii</i>, to open new avenues for the exploration of novel candidates to fight against drug-resistant <i>Acinetobacter baumannii</i>.</p> Graphical abstract <p></p> <p>This review outlines the current innovations of hybrid molecules with therapeutic potential against drug-resistant <i>A. baumannii</i> pathogens and discusses various aspects of structure–activity relationships.</p>