This review discusses the molecular pathogenesis, diagnosis, and therapeutic advances in melanoma. Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and high mortality. Recent molecular studies have identified key genetic and epigenetic changes that drive melanoma development, including mutations in BRAF, NRAS, c-KIT, and GNAQ/GNA11 genes. Diagnostic techniques such as genomics, transcriptomics, liquid biopsies, and molecular biomarkers have improved early detection and prognosis. Therapeutic advances include targeted therapies and immunotherapies, which have significantly improved patient outcomes. The review highlights the challenges of therapy resistance and the importance of personalized medicine. It explores novel treatment strategies such as neoantigen vaccines, adoptive cell transfer, microbiome interactions, and nanoparticle-based combination therapy. These approaches emphasize the need for evidence-based therapy selection in managing the increasing global incidence of melanoma. The review also discusses molecular pathways such as the MAPK/ERK and PI3K/AKT/mTOR pathways, which are crucial in melanoma progression. Additionally, it covers the role of melanogenesis and neuroendocrine regulation in melanoma progression. The review highlights the importance of molecular diagnostic techniques, including next-generation sequencing and liquid biopsies, in melanoma diagnosis and prognosis. It also discusses the role of molecular biomarkers in predicting treatment responses. The review outlines various molecular therapeutic strategies, including targeted therapy, immunotherapy, and combination therapies. It emphasizes the potential of novel approaches such as LAG-3 inhibitors and DNA damage response inhibitors in overcoming resistance and improving outcomes. The review concludes that while significant progress has been made in melanoma treatment, ongoing research is essential to address challenges such as therapy resistance, high costs, and limited accessibility. The integration of emerging therapies into clinical practice is crucial for improving patient outcomes and achieving more personalized and effective care.This review discusses the molecular pathogenesis, diagnosis, and therapeutic advances in melanoma. Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and high mortality. Recent molecular studies have identified key genetic and epigenetic changes that drive melanoma development, including mutations in BRAF, NRAS, c-KIT, and GNAQ/GNA11 genes. Diagnostic techniques such as genomics, transcriptomics, liquid biopsies, and molecular biomarkers have improved early detection and prognosis. Therapeutic advances include targeted therapies and immunotherapies, which have significantly improved patient outcomes. The review highlights the challenges of therapy resistance and the importance of personalized medicine. It explores novel treatment strategies such as neoantigen vaccines, adoptive cell transfer, microbiome interactions, and nanoparticle-based combination therapy. These approaches emphasize the need for evidence-based therapy selection in managing the increasing global incidence of melanoma. The review also discusses molecular pathways such as the MAPK/ERK and PI3K/AKT/mTOR pathways, which are crucial in melanoma progression. Additionally, it covers the role of melanogenesis and neuroendocrine regulation in melanoma progression. The review highlights the importance of molecular diagnostic techniques, including next-generation sequencing and liquid biopsies, in melanoma diagnosis and prognosis. It also discusses the role of molecular biomarkers in predicting treatment responses. The review outlines various molecular therapeutic strategies, including targeted therapy, immunotherapy, and combination therapies. It emphasizes the potential of novel approaches such as LAG-3 inhibitors and DNA damage response inhibitors in overcoming resistance and improving outcomes. The review concludes that while significant progress has been made in melanoma treatment, ongoing research is essential to address challenges such as therapy resistance, high costs, and limited accessibility. The integration of emerging therapies into clinical practice is crucial for improving patient outcomes and achieving more personalized and effective care.