Introduction: Malignant massive Pericardial Effusion (PE) with Tamponade is life threatening and prompts immediate manage-ment. Case Report: We report a case of massive malignant PE with Tamponade in a 40-year-old female with uncommon symptoms. She was immediately survived after an emergency Pericardiocentesis. It’s HPE analysis, confirms presence of Mesothelioma. With multi-modality approach - we extensively searched for primary source of malignancy with Specific blood tests, Pleural and pericardial Fluid analysis, CT thorax and Pulmonary angiograms, Upper GI endoscopy and Sigmoidoscopy. With all negative reports, then referred to Oncology center, where diagnosed as adjacent left lower lobe of lung Mesothelioma by PET Scan. Un-derwent successful Left Lung Lobectomy and clinical follow-up confirms recovery. Conclusion: Malignant Massive Pericardial Effusion with Tamponade is a serious condition. Primary goal of management is immediate Pericardiocentesis, followed by extensive search for Primary Metastatic Neoplastic locations. Survival rate increases with early diagnosis and prompt management.