A constitutively active serine/threonine kinase, casein kinase 2 (CK2) is involved in several physiological functions, such as DNA repair, apoptosis, and cell cycle control. New research emphasizes how critical CK2 is to the immune system's dysregulation in the tumor immune-microenvironment (TIME). The inhibition of immunological responses, including the downregulation of immune effector cells and the elevation of immunosuppressive proteins that aid in the development of tumor and immune evasion, has been linked to CK2 overexpression. CK2 maintains an immunosuppressive milieu that impedes anti-tumor immunity by encouraging the expressions and activities of immune checkpoint markers, regulating cytokines release, and boosting immune-suppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) to maintain immune evasion. It is a promising target for cancer treatment due to its complex role in immune regulation and oncogenic pathways. In this study, we address the therapeutic perspectives of targeting CK2 in oncotherapy and investigate the mechanisms by which it controls immunological responses in the TME. This review, comprehending the function of CK2 in immune suppression can facilitate the creation of innovative treatment approaches aimed at augmenting anti-tumor immunity and enhancing immunotherapy effectiveness.