Purpose of Review <p>This review aims to evaluate current treatment approaches for sporadic late-onset nemaline myopathy (SLONM) and explore how emerging omics data, particularly proteomics and transcriptomics, can contribute and optimize therapeutic strategies.</p> Recent Findings <p>SLONM presents with clinical and pathological variability and is frequently associated with monoclonal gammopathy of undetermined significance (MGUS), which can influence both disease progression and response to treatment. Standard therapies include immunosuppressive agents, intravenous immunoglobulin (IVIG), chemotherapy, and autologous stem cell transplantation (ASCT), with ASCT showing particularly favorable outcomes in MGUS-associated cases. Recent proteomic studies have identified distinct molecular patterns in SLONM, including altered expression of sarcomeric and immune-related proteins, as well as deposits of immunoglobulin light chains. Complementary transcriptomic data highlight immune dysregulation and metabolic stress as key contributors to disease pathology. Together, these findings support the development of omics-informed precision therapies that target plasma cell clones and immune pathways, offering improved patient stratification and more tailored treatment approaches.</p> Summary <p>Integrating omics data with clinical features deepens our understanding of SLONM pathogenesis and helps explain the variability in treatment responses. Targeted therapies—especially plasma cell-directed approaches in MGUS-positive patients and immunomodulatory strategies in MGUS-negative cases—are showing encouraging results. Future research should focus on validating omics-based biomarkers to refine diagnosis and support the development of personalized treatment protocols, ultimately improving outcomes in this rare but treatable muscle disorder.</p>