<p><i>Herpes simplex virus</i> (HSV) is attractive for oncolytic therapy due to its genetic capacity, effect on various tumors, ability to trigger immune responses, and adaptation to the cancer microenvironment. Its oncolytic potential can be enhanced by genetic modifications that help Herpes simplex virus escape adaptive immunity and better direct immune responses. While the virus replicates specifically in cancer cells, it does not harm normal cells. Effects like immunogenic cell death and cytokine release in the tumor microenvironment hinder immune invasion of cancer and improve treatment effectiveness. Oncolytic HSV (oHSV) therapy shows great potential both as an independent treatment and when combined with immune checkpoint inhibitors, Chimeric antigen receptor T cell therapies, and cytokines. The capacity of oHSV to remodel the tumor microenvironment, activate immune cells, and induce systemic antitumor immune responses contributes to its overall therapeutic efficacy, particularly in the treatment of metastatic cancers. Pre-clinical and clinical studies indicate that Herpes simplex virus -based virotherapy can be effective for certain cancers, including melanoma, head and neck cancers, and glioblastoma. The use of personalized elements in Herpes simplex virus, like neoantigens, tumor-specific promoters, and chemokines, offers exciting potential for tailored virotherapy. Ongoing research and biotechnological advances are expected to produce safer, more efficient treatments, fostering wider adoption of oHSV in cancer management. This study examines tumor-specific modifications of HSV advances in cancer therapies, and discusses the benefits, challenges, and recommendations for synergizing oHSV with other treatments.</p> Graphical abstract <p></p>