The opioid crisis, driven by illicitly manufactured fentanyl, presents significant challenges in treating opioid use disorder (OUD) and opioid withdrawal syndrome. Fentanyl is uniquely lethal due to its rapid onset and respiratory depressant effects, driving the surge in overdose deaths. This review examines the limitations of traditional diagnostic criteria like those of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) and explores the potential of dimensional models such as the Hierarchical Taxonomy of Psychopathology (HiTOP) for a more nuanced understanding of OUD. Current treatments, including medications for OUD, are evaluated for efficacy in managing fentanyl-related OUD. Innovations in drug formulations and alternative induction methods are discussed to address the unique challenges posed by fentanyl. Psychotherapeutic and behavioral interventions, such as cognitive behavioral therapy and contingency management, are highlighted as crucial complements to pharmacotherapy. The review underscores the need for increased precision, comprehensive phenotyping, and advanced diagnostics to develop personalized treatment plans, all with the aim of improving patient outcomes and mitigating the societal impact of the opioid crisis.