Gastrointestinal stromal tumors (GISTs) are one of the most prevalent non-epithelial tumors of the GI mesenchyme. While stromal tumors account for less than 1% of all malignancies, a knowledge of their etiology and signaling pathways can aid in identifying new molecular targets for the potential development of therapeutics. One of the drugs that have shown remarkable action against GIST is imatinib, a tyrosine kinase inhibitor (TKI).We present a case of a female patient with a long-term history of heart failure (HF) with preserved ejection fraction (EF) and minimal pericardial effusion who had recently started imatinib therapy and was hospitalized after new-onset atrial fibrillation (AF) and the development of significantly increased pericardial and pleural effusion. She had been diagnosed with GIST a year ago and started on imatinib. She presented to the ER with complaints of left-sided chest pain. ECG revealed a new AF. The patient was started on rate control and anticoagulation. After a few days, she returned to the ER with complaints of shortness of breath (SOB). The patient was found to have pericardial and pleural effusions on imaging. Fluids from both effusions were aspirated and sent to pathology to rule out malignancy. The patient developed recurrent bilateral pleural effusions after discharge, which were later drained on subsequent hospitalization.Although imatinib is generally well tolerated, it does cause both AF and pleural/pericardial effusions in rare cases. In such cases, it is essential to perform a thorough workup to rule out other possibilities such as metastasis, malignancy, or infection.