Cancer remains a significant challenge in modern medicine, prompting continuous exploration for novel therapeutic strategies. Understanding the complex molecular mechanisms driving cancer progression is essential for developing effective treatments. The RUVBL1/2 complex, formed by highly conserved AAA+ ATPases (ATPases associated with diverse cellular activities) RUVBL1 and RUVBL2 proteins, is known for its roles in chromatin remodeling, transcriptional regulation, and DNA repair. This complex has attracted significant attention for its potential as both prognostic marker and therapeutic target across various cancer types. This chapter explores the structural and functional hallmarks of the RUVBL1/2 complex in cancer pathogenesis, outlining its contribution to key cellular processes that promote tumorigenesis. We also discuss how RUVBL1/2 dysregulation drives oncogenic processes and confers selective advantages to cancer cells. Furthermore, we highlight its potential utility as a biomarker for cancer diagnosis and prognosis. Targeting the RUVBL1/2 complex offers anticancer activities with the potential to disrupt tumor cell proliferation and survival both in vitro and in vivo. Finally, we address the current progress in pharmacological inhibition of the RUVBL1/2 complex, emphasizing its promise for preclinical development and clinical translation in advancing personalized cancer therapy.