A network neuroscience perspective can significantly advance the understanding of neurodegenerative disorders, particularly frontotemporal dementia (FTD). This study employed an innovative multiplex connectomics approach, integrating cortical thickness (CTH) and fluorodeoxyglucose-positron emission tomography (FDG-PET) in a dual-layer model to investigate network alterations in FTD subtypes across two geographically distinct sites. The cohort included groups of behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), mild cognitive impairment (MCI), and cognitively normal (CN) individuals who were analyzed from two separate sites. Site 1 included 28 bvFTD, 20 PPA, and 27 MCI participants, whereas Site 2 included 26 bvFTD, 43 PPA, and 43 CN individuals, respectively. Utilizing CTH and FDG-PET data after standard preprocessing, a multiplex network pipeline in BRAPH2 toolbox was used to derive multiplex participation coefficient (MPC) between the groups. The analysis revealed an increase in global MPC as an indicator of disease in PPA at both sites. Additionally, nodal MPC alterations in the anterior cingulate, frontal, and temporal lobes in PPA were compared with bvFTD. Comparisons with the CN showed that nodal MPC alterations were more extensive in PPA when compared with bvFTD. These findings underscore the potential utility of multiplex connectomes for identifying network disruptions in neurodegenerative disorders, offering promising implications for future research and clinical applications. Author Summary This study uses multiplex connectomics, a method combining cortical thickness and glucose metabolism data, to investigate frontotemporal dementia (FTD) across two sites. Behavioral variant FTD (bvFTD) and primary progressive aphasia showed global and nodal brain network alterations. PPA exhibited more widespread disruptions in the anterior cingulate, frontal, and temporal lobes than bvFTD, suggesting greater network changes. bvFTD showed distinct alterations in the left caudal anterior cingulate and temporal pole compared with mild cognitive impairment and more extensive changes compared with cognitively normal individuals. These findings highlight the value of multiplex connectomics in identifying complex brain network changes in FTD and emphasize the need for further research to uncover the mechanisms behind these alterations.