<p>Anoikis (or cell detachment-induced apoptosis) is a mechanism used by organisms to protect themselves and eliminate “misplaced” cells in an inappropriate location. This mechanism is critical for maintaining tissue integrity and preventing cell migration. However, cancer cells resist anoikis and survive through metastasis. Elucidating the molecular mechanisms of anoikis resistance will lead to important potential strategies against cancer migration and metastasis, the epithelial mesenchymal transition (EMT) process, cell-cell junctions, and ECM-cell interactions, as well as the identification of personalized treatment options. In this review, we summarize the mechanisms of anoikis/anoikis resistance. We highlight recent advances in anoikis and how anoikis resistance manifests in normal and cancer cells. We also briefly discuss compounds targeting anoikis resistance, including nanoparticles, nanotherapies, and chemical inhibitors, and explain how emerging data can benefit treatment strategies. We highlight the techniques used in in vitro and in vivo models for the study of anoikis resistance, which play a significant role. Our overall goal is to pioneer studies targeting anoikis resistance, which plays a role in cancer metastasis, and to guide developments in treatment strategies and personalized patient-focused inference perspectives, which are expected to gain increasing importance in the coming years.</p> Graphical abstract <p></p>