Background:　Gray　matter　volume　(GMV)　alteration　in　specific　brain　regions　has　been　widely　regarded　as　one　of　the　most　important　neuroplasticity　features　in　chronic　pain　patients　with　depressive　symptoms　(CP-D).　However,　the　consistent　and　significant　results　were　still　lacking.　Thus,　further　exploration　was　suggested　to　be　performed.　Objectives:　This　study　aimed　to　comprehensively　collect　the　voxel-based　morphometry　(VBM)　studies　on　GMV　alteration　between　CP-D　and　healthy　controls　(HCs).　And　a　systemic　review　and　meta-analysis　were　made　to　explore　the　characteristic　brain　regions　in　chronic　pain　and　depression　comorbidity.　Methods:　Search　of　PubMed,　MEDLINE,　Web　of　Science,　and　Cochrane　Library　databases　updated　to　July　13,　2021.　The　altered　GMV　between　CP-D　and　HCs　in　VBM　studies　was　included　in　this　meta-analysis.　In　total,　18　studies　(20　datasets)　and　1320　participants　(520　patients　and　800　HCs)　were　included.　The　significant　coordinate　information　(x,　y,　z)　reported　in　standard　space　and　the　effect　size　(t-value　or　z-score)　were　extracted　and　analyzed　by　anisotropic　effect　size-signed　differential　mapping　(AES-SDM)　5.15　software.　Results:　According　to　the　main　analysis　results,　CP-D　showed　significant　and　consistent　increased　GMV　in　the　left　hippocampus　(HIP.　L)　and　decreased　GMV　in　the　medial　part　of　the　left　superior　frontal　gyrus　(SFG.　L,　BA　10)　compared　to　HCs.　Subgroup　analysis　showed　significant　decreased　GMV　in　the　medial　orbital　part　of　SFG.R　(BA　10)　in　neuropathic　pain,　as　well　as　significant　increased　GMV　in　the　right　parahippocampal　gyrus　(PHG.R,　BA　35),　left　hippocampus　(HIP.L,　BA　20),　and　right　middle　frontal　gyrus　(MFG.R)　in　musculoskeletal　pain.　Furthermore,　meta-regression　showed　a　positive　relationship　between　the　decreased　GMV　in　the　medial　part　of　SFG.L　and　the　percentage　of　female　patients.　Conclusion:　GMV　abnormality　in　specific　brain　areas　(e.g.,　HIP.L　and　SFG)　was　robust　and　reproducible,　which　could　be　significantly　involved　in　this　comorbidity　disease.　The　findings　in　this　study　may　be　a　valuable　reference　for　future　research.Systematic　Review　Registration[].