Chronic non-specific low back pain (CNSLBP) is a debilitating condition that affects millions of people worldwide, significantly impacting quality of life and imposing a substantial socioeconomic burden. Traditional treatment approaches often rely on a one-size-fits-all strategy, failing to account for individual variations in pathophysiological mechanisms, drivers, and the principles of personalized medicine. Furthermore, an overemphasis on biomechanical findings from imaging may lead to ineffective interventions and unnecessary surgical procedures, obscuring other important factors that contribute to pain perception. While highlighting the limitations of universal treatment approaches, in this review we present a practical clinical approach aimed at elucidating the main pathophysiological mechanisms and various factors underlying the development and maintenance of CNSLBP in order to create a personalized treatment program. In conclusion, this review underscores the need for personalized therapeutic strategies that take into account the unique characteristics of each patient, recognizing the complex interaction of biological, psychological, social, and other factors that contribute to the development of individual pain. By combining a comprehensive understanding of the complexities of this condition, we aim to improve clinical outcomes and provide information on the development of effective personalized treatment algorithms, particularly in the field of neurological practice.