Cutting-edge research elucidates genetic and epigenetic contributors to systemic sclerosis (SSc) and cancers. Single-cell RNA sequencing has identified immune cell subtypes linking to disease heterogeneity in SSc, while exome sequencing combined with machine learning revealed novel risk genes including MICB. In hepatocellular carcinoma, aberrant DNA methylation patterns disrupt tumor suppressor and oncogene regulation, revealing potential biomarkers and therapeutic targets. These advancements deepen molecular insights essential for precision medicine in autoimmune disorders and oncology.