Despite the shift toward a biopsychosocial paradigm of medicine, many physicians and mental health professionals (MHPs) find it difficult to treat patients with psycho-somatic disorders. This situation is particularly troublesome due to the high prevalence of these conditions. Although progress has been made over the last few decades in understanding mechanisms underlying the mind-body relationship, disparities remain between research and its clinical implementation. One possible reason for this is the lack of a comprehensive, agreed-upon model that incorporates a biopsychosocial framework and is rooted in an understanding of the various psychobiological pathways. Such a model would enable better communication between physicians and MHPs, allowing them to provide coordinated, stratified treatment. In this paper, four archetypal case studies, together with standard care options are presented to illustrate the current state of affairs. A four-tiered conceptual model of mind-body interrelationships based on pathophysiological and psychopathological mechanisms is suggested to help optimize the treatment of somatic complaints. This Four-Cluster model consists of: (1) Organic Conditions: Structural, or degenerative processes that can affect mood and psychological responses but are not clearly exacerbated by stress. (2) Stress Exacerbated Diseases: Biological disorders with a distinct pathophysiology, such as inflammatory or autoimmune diseases, whose progression is clearly exacerbated by stress. (3) Functional Somatic Syndromes: Conditions wherein heightened sensitivity to stimuli together with hyper-reactivity of the autonomic system form a "vicious cycle" of mutually enhancing learning processes. These processes involve biological mechanisms, such as central sensitization and psychological mechanisms such as catastrophization and selective attention. (4) Conversion Disorder: Physical manifestations of psychological distress, expressed somatically. Symptoms are solely an expression of problems in patients' psychic functioning and are not caused by biological pathology. Finally, suggested management of the aforementioned case studies is presented through the lens of the Four-Cluster model and a proposed integration of our model with existing theories is discussed. As it is rooted in an understanding of psychobiological pathways of illness, the proposed model enables a new way to discern which form of mind-body interaction is manifesting in different diseases and proposes a way to coordinate treatment plans accordingly, to enhance the accuracy and efficacy of care.