Urban China is witnessing a growth of migrant grandparents apart from the prevalent local grandparent caregiving. However, the health consequences and influencing factors of grandparent caregiving remain largely unknown among migrant and local grandparent caregivers. This study examined informal and formal social support’s mediation roles between domestic generative acts and life satisfaction, as well as investigating Hukou’s (household registration system) moderation effect. Our sample compromised 1013 grandparent caregivers (Migrant = 508, Local = 505) from 12 kindergartens with a multistage clustered random sampling from Eastern China. Migrant grandparent caregivers had significant lower informal social support (M = 4.000, L = 4.355, p < 0.001), formal social support (M = 1.787, L = 2.111, p < 0.001), and life satisfaction (M = 3.323, L = 3.574, p < 0.001) than local ones. Structural equation modeling results indicated that domestic generative acts positively associated with life satisfaction (b = 0.085, p < 0.05), informal (b = 0.223, p < 0.001) and formal social support (b = 0.080, p < 0.05); informal (b = 0.379, p < 0.001) and formal social support (b = 0.138, p < 0.001) positively associated with life satisfaction. In addition, both informal (β = 0.084, CI [0.039, 0.101], p < 0.001) and formal social support (β = 0.011, CI [0.001, 0.018], p < 0.05) mediated the relationship between domestic generative acts and life satisfaction. Furthermore, Hukou status moderated the indirect path from domestic generative acts to life satisfaction via informal social support (p < 0.01), but not formal social support (p > 0.05). Migrant grandparent caregivers, with limited formal social support resources, were found to be more dependent on informal social support than locals. The findings revealed social support and wellbeing disparities among migrant and local grandparent caregivers in urban China. Theoretical contributions and practical implications are also discussed.