Health-based neuroscience is a relatively recent field that straddles the lines between neuroscience and psychology. Particularly, stress is recognized as a significant issue in preclinical and applied neuroscience studies. Numerous studies have established the knowledge in the realm of stress. Subsequently, it was established that the stressing system, which incorporates a wide variety of brain structures capable of detecting events and interpreting them as real or prospective dangers, elaborates and triggers the reaction to stressful situations. Nevertheless, various kinds of stressors engross diverse brain networks, necessitating a fine-tuned function-based neuroanatomical process. This combination of information develops the stressor itself that results in a hasty stimulation of the Sympathetic-Adreno-Medullar and the Hypothalamus-Pituitary-Adrenal axes, the 2 main components convoluted in the stress response. The stress-responsive intricacy is not limited to neuroanatomy or SAM and HPA axes intermediaries, but also different as per timing and extent of stressor exposure, along with its shorter or longer-term effects. The investigation of stress-related neuronal circuits alongside their interface with mediator molecules over a period is perilous, not just for understanding physiological stress reactions and also for comprehending their consequences for mental illnesses.