Abstract
Melanoma, a highly aggressive form of skin cancer, is shaped by a complex interplay of genetic, environmental, and lifestyle factors. This review provides a comprehensive synthesis of the macroscopic and molecular mechanisms through which various factors such as gender, age, obesity, smoking, alcohol consumption, diet and nutrients, exercise, ultraviolet (UV) exposure, circadian rhythms, and commonly used medications (e.g., steroids, metformin, non-steroidal anti-inflammatory drugs [NSAIDs], and antihistamines), impact melanoma risk, progression, and outcomes. To facilitate a more systematic understanding of melanoma risk and pathogenesis, a comprehensive framework is proposed that delineates these factors into four major categories: intrinsic host characteristics, pharmacological influences, metabolic conditions, and behavioral risk profiles. Within each category, these elements interact at the molecular level, collectively influencing the initiation and progression of melanoma. Furthermore, the translational implications of these findings are evaluated, offering actionable insights for prevention and therapeutic strategies in clinical practice. This review aims to bridge the gap between molecular research and real-world behavioral determinants, providing a holistic framework that advances our understanding of melanoma pathogenesis and supports the development of improved clinical outcomes.