Alexithymia is a disorder that stands at the border of mind and body, with psychological/affective and physiological/experiential disturbances. The purpose of this article is to propose a new clinical access point for the evaluation and treatment of the deficits in emotional awareness demonstrated in alexithymia. This will be based on insights from recent neuroscientific research, which is adding to the psychodynamic understanding of alexithymia, regarding clinical presentation and etiology. Following a brief review of definitions, forms of measurement, and potential etiologic elements of alexithymia, current neuroscientific theory and research into “predictive processing” approaches to brain function will be outlined, including how “interoception” and “interoceptive inference” underpins emotion and emotional awareness. From this synergistic perspective, I will outline how interoceptive inference provides a key to the link between: problems in early life relational experiences and the patient’s long held, but suboptimal models of their inner and outer world. This is reflected in the deficits in affective experiencing and emotional awareness described in alexithymia. Three clinical cases will be presented to illustrate this nuanced consideration of alexithymic etiology and treatment. The implications of the historical, psychological, and somatic aspects of experience will be considered, regarding the patients’ diminished ability to: experience and represent emotional experience as distinct feeling states; signify the relevant meaning of affective experience; and incorporate such with cognitions to adaptively guide behavior. These will be addressed using psychometric, psychological, neuro-cognitive, and neurocomputational approaches. Elements from current theory, research, and treatment of alexithymia, will be highlighted that are salient to the clinician, in order to support their understanding of patients against the backdrop of current psychodynamic and neuroscientific research, which will thereby increase treatment options and benefits. The focus, and conclusion, of this article is the role that attention to interoception can play (within the safety of the therapeutic relationship and within any therapeutic process) in allowing updating of the patient’s strongly held but dysfunctional beliefs.