Background <p>The mental health of migrants living in the post-migration urban environment poses a significant public health challenge in both developed and developing economies. Few empirical studies attempted to disentangle the influence pathways that acculturation might produce the link between the residential environment and health effects.</p> Methods <p>Data from 385 migrants was collected using a multi-stage stratified sampling method from 25 communities in Yiwu, China. We used a multi-level regression model and conditional process analysis to examine the health effects of the perceived neighbourhood environment and influence pathways of acculturation.</p> Results <p>The results found that participants’ mental health was moderate (mean = 15.9 out of 24). Migrants residing in relocation neighbourhoods and factory dormitories exhibit significantly lower mental health. The neighbourhood effects of migrant-dominated, local-dominated, and mixed residential neighbourhoods contribute positively to migrants’ mental health. Neighbourhood physical environment positively affects mental health, whereas the neighbourhood social environment negatively affects mental health. Moreover, EGS (β_indirect=-0.04, BootLLCI=-0.096, BootULCI=-0.002) and NSC (β_indirect=-0.038, BootLLCI=-0.081, BootULCI=-0.007) impact migrants’ mental health through the mechanism of acculturative stress. Migrants in the assimilation group experienced reduced acculturative stress as the NFA (β=-0.377, <i>p</i> = 0.035) improved. In contrast, those in the separation group faced increased acculturative stress as the improvements of NFA (β = 0.392, <i>p</i> = 0.05) and EGS (β = 0.809, <i>p</i> = 0.027).</p> Conclusions <p>These findings suggest that future public health intervention strategies should be considered for improved neighbourhood environments, promoted residential integration, alleviated acculturative stress and prioritised acculturation strategies to enhance rural migrants’ mental health.</p>