AimsThis case report aimed to discuss the multifactorial etiology and also the management of temporomandibular disorders (TMD) by addressing important associated psychosocial and biological factors, emphasizing the interaction between these factors and a probable genetic predisposition.Methods and resultsA 21‐year‐old female patient was evaluated according to Research Diagnostic Criteria for TMD and diagnosed with arthralgia, myofascial pain, disc displacement without reduction, and temporomandibular joint (TMJ) degenerative disease. TMJ alterations were confirmed through magnetic resonance imaging and cone‐beam computed tomography. Pressure pain threshold of masticatory structures was evaluated using a pressure algometer. Sleep bruxism, poor sleep quality, migraine with aura, mild anxiety, and history of facial trauma were also identified through anamnesis and clinical examination. Following this, genetic analysis was performed to evaluate the presence of single nucleotide polymorphisms (SNPs) already associated with TMD: SNP COMT Val158Met (rs4680), MMP1‐1607 (rs1799750), and tumor necrosis factor alpha‐308 (rs1800629), which were all present. A personalized treatment for TMD management was performed, and it included self‐management programs, occlusal appliance therapy, pharmacotherapy, anxiety management, and stress control. An 8‐year follow‐up demonstrated long‐term stabilization of TMJ degenerative disease.ConclusionGenetic evaluation, added to anamnesis and clinical examination, could be useful for TMD prognosis and management.