Alcohol and nicotine intake result in neurological alterations at the circuit level. Resting state functional connectivity has shown great potential in identifying these alterations. However, current studies focus on specific seeds and leave out many brain regions where effects might exist. The present study uses a data driven technique for brain segmentation covering the whole brain. Functional magnetic-resonance-imaging (fMRI) data were collected from 188 subjects:51 non-substance consumption controls (CTR), 36 smoking-and-drinking subjects (SAD), 28 drinkers (DRN), and 73 smokers (SMK). Data were processed using group independent component analysis to derive resting state networks (RSN). The resting state functional network connectivity (rsFNC) was then calculated through correlation between time courses. One-way ANOVA tests were used to detect rsFNC differences among the four groups. A total of 50 ANOVA tests were significant after multi-comparison correction. Results delineate a general pattern of hypo-connectivity in the substance consumers. Precuneus, postcentral gyrus, insula and visual cortex were the main brain areas with rsFNC reduction suggesting reduced interoceptive awareness in drinkers. In addition, connectivity reduction between postcentral and one RSN covering right fusiform and lingual gyri showed significant association with severity of hazardous drinking. In smokers, connectivity changes agreed with the idea of a shift towards endogenous information processing, represented by the DMN. Hypo-connectivity between thalamus and putamen was observed in smokers. In contrast, the angular gyrus showed hyper-connectivity with the precuneus linked to smoking and significantly correlated with nicotine dependence severity. In spite of the presence of common effects, our results suggest that particular effects of alcohol and nicotine can be separated and identified. Results also suggest that concurrent use of both substances affects brain connectivity in a complex manner, requiring careful consideration of interaction effects.