Chromosomal instability (CIN) is now recognized as an essential characteristic underlying cancer evolution. On the other hand, cancer immunoediting is believed to shape the immunogenicity of malignancy in such a way that may lead to the generation of variants leading to evasion of host immunity. It is thus logical to predict that the above two act together to draft the ultimate fate of a malignancy. Although the link between the above two events was established in the recent two decades, the exact mechanisms remain somewhat elusive. CIN has been demonstrated to trigger the innate immune response primarily via activating the cGAS-STING-Type I IFN axis through micronuclei, which can act against the ongoing malignant process. However, if the process continues for a long time, the nature of the immune response tilts to pro-tumor, with immunosuppressive phenotypes and molecules playing a dominant role. However, besides the duration of CIN, other factors governing the effect of CIN-induced immunity in cancer need to be identified. Due to its role in CIN-induced immunity, the cGAS-STING pathway is extensively explored from the therapeutic point of view. STING agonists are already in different phases of clinical trials involving their combinations with other agents. Apart from cGAS-STING, the role of other dsDNA sensor molecules in CIN-induced immunity is also attracting attention. The link between CIN-induced immunity and tumor mutational burden, its influence on therapeutic response to immune checkpoint inhibitors, and other prognostic parameters in malignancies are some of the attractive topics for future studies.