Chronic lymphocytic leukemia (CLL) is a slow-growing cancer affecting older adults. About 10% of CLL cases transform into a fast-growing, aggressive type called Richter’s transformation (RT), which is resistant to treatment and has poor survival rates. Current treatments for RT are limited, underscoring the need for new strategies. Our research focuses on RT cell metabolism. We found that RT cells rely heavily on a specific energy pathway called oxidative phosphorylation (OXPHOS). Targeting OXPHOS in our mouse models improved survival, suggesting it could be an effective treatment approach. Hence, we aim to identify specific therapeutic vulnerabilities to develop better-targeted therapies for patients.