In the last years, cancer immunotherapies have revolutionized cancer treatment paradigms, in this scenario, oncolytic virus-based solutions showed potentials thanks to their ability to induce the immunogenic cell death (ICD), a process that make neoplastic cells visible to the adaptive immune system for the release in the tumor microenvironment of neoantigens (NeoAg), tumor-associated antigens (TAAs), danger-associated molecular pattens (DAMPs). However, the employment of oncolytic viruses in clinical trials is hampered by several drawbacks such as the induction of antiviral immunity, the lack of a precise control of their virulence and the absence of exclusive specificity toward cancer cells. Thus, an innovative perspective is offered by nanotechnology, in particular, bio-engineered nanoparticles (NPs) represent an extremely promising tool for the production of multimodal ICD nanoplatform that could act as synthetic oncolytic nanovaccine, in order to facilitate a safe, specific and effective ICD-triggered antitumor immunity.