Femoral fractures represent a major global orthopedic burden, particularly among elderly and osteoporotic populations, and are associated with substantial morbidity, mortality, and healthcare costs. Intramedullary fixation, in which a metallic nail is inserted into the medullary canal to stabilize fractured bone, remains the clinical gold standard because it provides load-sharing stabilization through a minimally invasive approach. Nevertheless, implant–bone mismatch, cortical impingement, fixation instability, infection, and delayed osseointegration continue to compromise long-term outcomes owing to patient-specific anatomical variability, age-related skeletal remodeling, and the limited biological activity of conventional implants. This review provides a comprehensive overview of femoral isthmus morphology, age-dependent anatomical remodeling, and their implications for personalized intramedullary fixation. Particular emphasis is placed on recent advances in functional biomaterials designed to improve implant performance and bone regeneration. Representative strategies include bioactive ceramic coatings (e.g., barium titanate and hydroxyapatite), piezoelectric ceramics, electroactive polymers such as poly (vinylidene fluoride) and poly (L-lactic acid), nanostructured coatings, antibacterial interfaces, multifunctional composite scaffolds, and ultrasound-responsive platforms. These materials have demonstrated the ability to regulate osteoblast proliferation and differentiation, enhance osseointegration, modulate inflammatory responses, inhibit bacterial colonization, and accelerate bone healing by providing biochemical, topographical, and electromechanical stimulation at the bone–implant interface. Furthermore, this review discusses emerging technologies, including additive manufacturing, artificial intelligence-assisted implant design, digital twin modeling, shape-adaptive materials, and patient-specific fixation strategies, which collectively offer new opportunities for precision orthopedic care. By integrating advances in femoral anatomy, biomechanics, materials chemistry, nanotechnology, and piezoelectric bioengineering, this review highlights the development of intelligent and multifunctional intramedullary fixation systems that improve implant integration, promote bone regeneration, and address the growing clinical demands of an aging population.