Osteoarthritis (OA) has emerged as a significant public health crisis in Latin America, with prevalence rates in Mexico doubling over the last two decades. Despite this growing burden, current management in underrepresented populations —defined here as groups facing structural barriers to care, including rural or remote communities, uninsured individuals, and socioeconomically disadvantaged groups —is hindered by a critical mismatch between international guidelines and regional healthcare realities. This narrative review, synthesized under the SANRA framework, evaluates the last 20 years of evidence to address the structural and clinical barriers that sustain a 50% diagnostic gap at the primary care level and high rates of inadequate pain relief. Using Mexico as a primary case study, we move beyond conventional symptomatic treatment to explore the complex interplay of central sensitization, neuroinflammation, and metabolic phenotypes, factors often overlooked in standardized protocols. By identifying the limitations of current pharmacological reliance and the underutilization of non-pharmacological interventions, this work proposes a strategic shift toward a multidisciplinary, patient-centered model. We outline a translational roadmap that integrates multi-omic research with personalized therapeutic strategies, emphasizing the need for evidence-based clinical practice guidelines tailored to the socioeconomic and genetic contexts of Latin American patients. Ultimately, this review serves as a call to action to bridge the healthcare disparity gap, offering a framework for innovative, integrative care to transform long-term clinical outcomes in developing healthcare systems.