Morphea, also known as localized scleroderma, is an autoimmune chronic connective tissue disease. It is characterized by excessive collagen deposition in the dermis and/or subcutaneous tissue. The etiopathogenesis of this disease is not fully understood, with endothelial cell damage, immunological disorders, extracellular matrix disorders and factors such as infection, trauma and other autoimmune diseases being considered. As medicine advances, there is increasing evidence that genetic factors play a significant role in disease risk and progression. In addition to environmental factors and genetic predisposition, epigenetic factors may be potential triggers for morphea. Epigenetics studies changes that affect gene expression without altering the DNA sequence, such as microRNAs, long non-coding RNAs or DNA methylation. Understanding the pathogenesis of this disease is key to identifying potential new treatments. There are anecdotal reports of good therapeutic effects following the use of biological drugs such as tocilizumab, a humanized IgG monoclonal antibody; abatacept, a recombinant soluble fusion protein; JAK inhibitors, such as tofacitinib and baricitinib; and a drug used successfully in cancer treatment, imatinib, a tyrosine kinase receptor inhibitor. In this article, we aim to review up-to-date knowledge on the pathogenesis of morphea, with particular emphasis on genetic and epigenetic factors. In addition, we present the new options of morphea treatment based on several case series treated with new drugs that are potential targets for the development of therapies for this disease.