Dermatomyositis (DM) is an immune-mediated inflammatory myopathy that can present with proximal muscle weakness and characteristic skin findings. Nuclear matrix protein 2 (NXP-2)-positive DM, while rare, has a strong association with malignancy. It can display features such as muscle weakness, subcutaneous edema, and refractory dysphagia, all of which were present in our 63-year-old male patient. He experienced a prolonged hospitalization and percutaneous endoscopic gastrostomy (PEG) tube placement. He improved with prednisone, azathioprine, rituximab, and intravenous immunoglobulin (IVIG) treatments. For over two years, he has had no evidence of malignancy. This case underscores the complexity of NXP-2-positive DM and the potential for severe presentations that may require the usage of second-line therapies.