Protein kinase 2 (CK2) is an enzyme ubiquitously present and exhibits extensive kinase activity. It has been strongly linked to tumor progression through the abnormal phosphorylation of key proteins. Research has consistently demonstrated that CK2 is deregulated in various cancer types, with enhanced protein expression and nuclear distribution in tumor cells. CK2 plays a crucial role in a complex network that promotes cell infiltration, migration, proliferation, apoptosis, and cancer progression through multiple pathways, including PI3K/AKT, JAK2/STAT3, ATF4/CDKN1, and HSP90/Cdc37. In addition to its role in cancer growth, there is mounting evidence that CK2 may also affect the immunological dynamics of cancer by altering immune cell functions within the tumor microenvironment, thus facilitating tumor immune evasion. Recent research has increasingly focused on CK2, recognizing it as a therapeutic objective for oncological interventions. This review will critically examine the structure and signaling pathways of CK2, highlighting the significance of further research aimed at enhancing our understanding of the CK2 machinery. Finally, we conclude by refining therapeutic options, notably transitioning from non-pharmacological techniques to strategic CK2 inhibitor use. This development shortens the path to the desired outcome, establishing a pioneering standard in cancer therapy.