<p>Necroptosis represents a distinct form of programmed cell death that exhibits characteristics of both necrosis and apoptosis. Due to its potential to activate anti-cancer immune responses, utilizing necroptosis to enhance immune activity within the tumor microenvironment has garnered significant attention. However, effectively regulating necroptosis in cancer remains a formidable challenge. Epigenetic, post-transcriptional and post-translational modifications are three primary mechanisms that alter molecular expression patterns without changing DNA sequence, playing crucial roles in cancer progression. While these modifications have been shown to significantly influence cancer development, their specific roles in regulating necroptosis in cancer have not been systematically elucidated. This review explores the role and mechanism of epigenetic, post-transcriptional and post-translational modification in the regulation of necroptosis in cancer, identifying potential regulatory targets and their therapeutic implications, thereby providing systematic theoretical support for necroptosis as an emerging target for cancer therapy.</p>