The aberrant expression of the zinc finger protein 217 (ZNF217) promotes multiple malignant phenotypes, such as replicative immortality, maintenance of proliferation, malignant heterogeneity, metastasis, and cell death resistance, via diverse mechanisms, including transcriptional activation, mRNA N-methyladenosine (mA) regulation, and protein interactions. The induction of these cellular processes by ZNF217 leads to therapeutic resistance and patients' poor outcomes. However, few ZNF217 related clinical applications or trials, have been reported. Moreover, looming observations about ZNF217 roles in mA regulation and cancer immune response triggered significant attention while lacking critical evidence. Thus, in this review, we revisit the literature about ZNF217 and emphasize its importance as a prognostic biomarker for early prevention and as a therapeutic target.