The use of invasive and non-invasive brain stimulation and neuromodulation technologies combined with neuroimaging approaches can help refine with causal evidence our physiopathological understanding of the Obsessive-Compulsive Disorder (OCD). Two key structures, the Orbitofrontal Cortex (OFC) and the Anterior Cingulate Cortex (ACC) have been found dysfunctional in OCD compared to healthy volunteers and on such basis have been tested as therapeutic targets for invasive and non-invasive neuromodulation therapy. Hereinafter, evidence addressing the cognitive processes subtended by to those two brain regions and their role in wider associated cortico-subcortical networks is reviewed. Very specifically, their relevance for OCD clinical features is discussed in extenso and its modulation with invasive and non-invasive focal brain stimulation such as deep brain stimulation (DBS) or transcranial magnetic Stimulation (TMS). Most importantly, this article brings new insights bridging causal evidence on the structural and functional neuroanatomy subtending OCD and novel therapeutic perspectives based on focal brain stimulation.