<p>Anoikis, a form of programmed cell death triggered by detachment from the extracellular matrix (ECM), maintains tissue homeostasis by removing mislocalized or detached cells. Cancer cells, however, have evolved multiple mechanisms to evade anoikis under conditions of ECM detachment, enabling survival and distant metastasis. Studies have identified differentially expressed proteins between suspended and adherent cancer cells, revealing that key metabolic and signaling pathways undergo significant alterations during the acquisition of anoikis resistance. This review explores the regulatory roles of epithelial-mesenchymal transition, cancer stem cell characteristics, metabolic reprogramming, and various signaling pathway alterations in promoting anoikis resistance. And the corresponding reagents and non-coding RNAs that target the aforementioned pathways are reviewed. By discussing the regulatory mechanisms that facilitate anoikis resistance in cancer cells, this review aims to shed light on potential strategies for inhibiting tumor progression and preventing metastasis.</p>