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Aim Substance use disorders (SUDs) are highly comorbid with post-traumatic stress disorder (PTSD). PTSD-SUD comorbidity is associated with greater functional impairments and relapse risk. Women with SUDs experience markedly higher rates of trauma and PTSD compared to men with SUDs, particularly due to sexual and domestic abuse. Despite the strong association between trauma exposure and SUDs, the neurobiological correlates are understudied, particularly among females with SUDs. However, there is indication of abnormal somatic and interoceptive processing in women with PTSD. The present study examines interoception-linked differences in intrinsic brain networks in a group of women with SUDs and varying histories of trauma exposure, some of whom have a current PTSD diagnosis. Methods Pre-intervention data were analyzed from a subset (N = 43) of women in SUD residential treatment recruited for a mindfulness-based intervention efficacy clinical trial. Participants diagnosed with PTSD (n = 14) or not (n = 29) performed a task which involved attending to the somatic and visceral sensations of the breathing cycle (interoception) while undergoing a functional MRI (fMRI) scan. FMRI analysis employed independent components analysis and dual regression. First, we assessed differences in functional connectivity of interoception-modulated functional networks among those with and without PTSD. Second, we tested associations between network strength and lifetime sexual violence exposure across all participants on networks that showed significant group differences. Results PTSD diagnosis was associated with reduced functional connectivity of an orbitofrontal network with the precuneus, mid-posterior insula, lateral prefrontal cortex and angular gyrus. OFC network strength was inversely associated with sexual violence exposure over-and-above the contribution of PTSD status alone. Conclusions Our findings provide a novel network-level account of brain activity associated with PTSD among women with SUDs, which may inform treatment response in this subpopulation., Highlights • FMRI correlates of interoceptive attention in women with substance use disorder (SUD) and post-traumatic stress (PTSD) • Task-based data analyzed using independent components analysis and dual regression • Reduced orbitofrontal network connectivity with insula and frontoparietal regions in SUD_PTSD comorbidity compared to SUD • Functional networks associated with exteroception did not distinguish PTSD-SUD from SUD-only • Severity of sexual trauma exposure is inversely associated with orbitofrontal network strength beyond PTSD status