Sometimes when cancers are being treated, a rare albeit possibly hazardous complication called tumor lysis syndrome (TLS) arises. Acute renal failure, neurologic complications, seizures, cardiac dysrhythmia, or death are some of the consequences of leaving TLS untreated. Generally, tumor lysis syndrome is seen in patients who are diagnosed with hematologic malignancies that have a rapid growth rate and are going through effective therapies. Historically, it has been found that both the growth rate and responsiveness of chronic lymphocytic leukemia (CLL) to chemotherapy are slow. Due to this, there have been fewer instances in which patients diagnosed with CLL suffered from TLS. As of recently, the B-cell lymphoma-2 protein inhibitor, venetoclax, and the oral kinase inhibitors, idelalisib, and ibrutinib are among the newly approved targeted treatments of CLL. Various other treatment therapies, as well as strategies combining these agents, are being worked on. The diagnosis, prevention, and management of tumor lysis syndrome were examined in this review. The TLS experience in CLL clinical trials with the newer agents was also summarized in a review. Overall, even though the risk posed by TLS was minor, the results could be very lethal. Hence, monitoring the patients was of utmost importance. In order to treat CLL, a lot of research was conducted regarding combination regimens and therapies which evoked quicker reactions. It could also result in an increased danger of TLS. For optimum management, careful observation and prophylaxis, alongside proper tests and management to amend laboratory abnormalities were required for patients who were in danger of TLS as they allowed safe and successful disease control.