Nowadays, the term ‘hybrid drugs’ come to have recognition in the pharmaceutical field as they can potentially overcome most of the pharmacokinetic drawbacks and used in the treatment of many diseases. Discovery of hybrid anticancer drugs with high therapeutic activity leads to trigger two or more cytocidal pharmacological mechanisms of action acting in synergy to inhibit tumor growth. The review showcases the research that is at the prime edge of hybrid anticancer drug discovery. Isoxazole and its derivatives are an important class of heterocyclic compounds show a broad spectrum of biological activities which have made them significant structures. A modification in their structures by incorporating heterocyclic ring to the isoxazole moiety has offered a high degree of diversity that has manifest beneficial for the discovery of hybrid molecules of isoxazole derivatives with potent activity. Thus this review explains the various synthesis of different isoxazole hybrid molecules and their evaluation of the anticancer activity.