Conceptually, modulation of non-apoptotic regulated cell death (RCD) by nanomaterials is a feasible anticancer strategy. Although the field faces a wide array of challenges, the pace of its development is impressive. Ample evidence suggests that induction of non-apoptotic RCDs helps overcome apoptosis resistance and adjust antitumor immunity. In this chapter, the current advances in the application of nanomaterials as RCD modulators are illustrated with a focus on metal and metal-based nanoparticles (NPs). It is particularly emphasized that induction of lytic RCDs like ferroptosis, necroptosis, pyroptosis, and PANoptosis holds great promise in cancer treatment. These RCDs are strongly immunogenic. Emission of immunogenic signals by cells dying via lethal subroutines associated with lytic morphology enhances antitumor immunity, which underscores the immunotherapeutic potential of targeting lytic RCDs. Arguably, the analysis of the available studies shows that reactive oxygen species (ROS) signaling is shown to play a pivotal role in induction of ferroptosis, necroptosis, pyroptosis, and PANoptosis by a broad range of NPs. However, it is still not clear how ROS interact with other components of the cell death machinery for selection of a particular cell death pathway. Although multiple challenges and drawbacks of targeting RCDs by nanodrugs in cancer have to be overwhelmed, it can be assumed that RCD-based nano-immunotherapy can enhance the effectiveness of anticancer treatment.