Background: Non-valvular atrial fibrillation (NVAF), the most prevalent cardiac arrhythmia globally, poses a dual challenge of thromboembolic and bleeding risks, with stroke being the most devastating complication. Despite advancements in anticoagulation and rhythm control, patient outcomes remain suboptimal. Aim: This review synthesizes current evidence on the pathophysiological mechanisms, multidimensional management strategies, and emerging innovations in NVAF to inform clinical practice and future research directions. Methods: A systematic literature search was conducted across nine databases (CNKI, Wanfang, SinoMed, VIP, PubMed, Web of Science, Cochrane Library, Embase, and MEDLINE) using combined Medical Subject Headings (MeSH) and free-text terms, including “atrial fibrillation,” “non-valvular atrial fibrillation,” “risk factors,” and “mechanism” (and their Chinese equivalents). Studies on NVAF pathogenesis, therapeutic interventions, and risk stratification tools were analyzed. Results: (1) Risk Factors and Pathophysiology: NVAF progression is driven by hemodynamic stress (e.g., hypertension), metabolic disorders (e.g., obesity, diabetes), chronic inflammation, and fibrosis. Biomarkers such as CRP and Galectin-3, along with TGF-β/Smad signaling, are central to atrial remodeling. (2) Anticoagulation Controversies: While NOACs reduce stroke risk compared to warfarin (HR = 0.79), challenges persist in extreme body weight populations and drug-drug interactions (e.g., with P-glycoprotein inhibitors). (3) Left Atrial Appendage Closure (LAAC): LAAC demonstrates non-inferiority to anticoagulation in stroke prevention (HR = 0.79) with reduced major bleeding (HR = 0.49), though device-related thrombosis (1.8–7%) remains a concern. (4) Precision Medicine: AI-driven models enhance stroke prediction (AUC = 0.71; sensitivity 92%), while genotype-guided warfarin dosing shortens INR stabilization by 40%. (5) Lifestyle Interventions: Combined Mediterranean diet and moderate exercise reduce AF burden (HR = 0.69) and reverse left atrial enlargement (LAVI reduced by 12%). (6) Multidisciplinary Care: Integrated “heart-brain team” approaches combining LAAC and PFO closure lower annual stroke recurrence from 8.2% to 2.1%, while comprehensive rehabilitation improves functional capacity (6MWD + 45 m) and quality of life (SF-36 + 12 points). Conclusion: NVAF management has evolved from isolated anticoagulation to a multidimensional paradigm integrating genomics, AI, and lifestyle modification. Future priorities include validating long-term outcomes of novel therapies, addressing evidence gaps in special populations, and implementing digitally enabled, cross-disciplinary care models to mitigate the global burden of NVAF-related complications.