Stress-related pathophysiology drives comorbid trajectories that elude precise prediction. Allostatic load algorithms that quantify biological "wear and tear" represent a comprehensive approach to detect multisystemic disease processes of the mind and body. However, the multiple morbidities directly or indirectly related to stress physiology remain enigmatic. Our aim in this article is to propose that biological comorbidities represent discrete pathophysiological processes captured by measuring allostatic load. This has applications in research and clinical settings to predict physical and psychiatric comorbidities alike. The reader will be introduced to the concepts of allostasis, allostasic states, allostatic load, and allostatic overload as they relate to stress-related diseases and the proposed prediction of biological comorbidities that extend rather to understanding psychopathologies. In our transdisciplinary discussion, we will integrate perspectives related to (a) mitochondrial biology as a key player in the allostatic load time course toward diseases that "get under the skin and skull"; (b) epigenetics related to child maltreatment and biological embedding that shapes stress perception throughout lifespan development; and
(c) evolutionary drivers of distinct personality profiles and biobehavioral patterns that are linked to dimensions of psychopathology.