Malignant pericardial effusion (MPE) is a progressive fluid accumulation in the pericardial space that can lead to pericardial tamponade. Despite the high recurrence rate associated with pericardiocentesis, it remains the mainstay therapy. Bleomycin has emerged as an intrapericardial sclerosing therapy that may reduce recurrence and improve patients' quality of life. This systematic review aimed to assess the efficacy and safety profile of Bleomycin instillation in patients with MPE. An exhaustive search was conducted in PubMed, Web of Science, Scopus, ProQuest, EBSCO, and ClinicalTrials.gov databases. Eligible studies included MPE patients as participants who were treated with intrapericardial Bleomycin, reporting the patients' outcomes and using English in the full text. Individual studies were assessed for quality using the Newcastle-Ottawa Scales for cohort studies and the Jadad Scale for trial studies. Eight studies were included in this systematic review involving 242 MPE patients treated with Bleomycin. Bleomycin demonstrated lower recurrence rates than other sclerosing agents, with only ≤5% of patients requiring repeated drainage due to recurrence. Bleomycin treatment resulted in 3.5 days less hospitalisation compared to doxycycline. Bleomycin is also safe to use, with reported less severe pain compared to other treatment agents for MPE, such as doxycycline and pericardiocentesis. Bleomycin may benefit patients by reducing recurrence rates and improving patients' quality of life. Moreover, it is safe and has low rates of adverse events following the instillation.