Regional acclimatisation and microbial interactions significantly influence the resilience of reef-building corals facing anthropogenic climate change, allowing them to adapt to environmental stresses. However, the connections between community structure and microbial interactions of the endemic coral microbiome and holobiont acclimatisation remain unclear. Herein, we used generation sequencing of internal transcribed spacer (ITS2) and 16S rRNA genes to investigate the microbiome composition (Symbiodiniaceae and bacteria) and associated potential interactions of endemic dominant coral holobionts (Pocillopora verrucosa and Turbinaria peltata) in the South China Sea (SCS). We found that shifts in Symbiodiniaceae and bacterial communities of P. verrucosa were associated with latitudinal gradient and climate zone changes, respectively. The C1 sub-clade consistently dominated the Symbiodiniaceae community in T. peltata; yet, the bacterial community structure was spatially heterogeneous. The relative abundance of the core microbiome among P. verrucosa holobionts was reduced in the biogeographical transition zone, while bacterial taxa associated with anthropogenic activity (Escherichia coli and Sphingomonas) were identified in the core microbiomes. Symbiodiniaceae and bacteria potentially interact in microbial co-occurrence networks. Further, increased bacterial, and Symbiodiniaceae α-diversity was associated with increased and decreased network complexity, respectively. Hence, Symbiodiniaceae and bacteria demonstrated different flexibility in latitudinal or climatic environmental regimes, which correlated with holobiont acclimatisation. Core microbiome analysis has indicated that the function of core bacterial microbiota might have changed in distinct environmental regimes, implying potential human activity in the coral habitats. Increased bacterial α diversity may lead to a decline in the stability of coral-microorganism symbioses, whereas rare Symbiodiniaceae may help to retain symbioses. Cladocopium, γ-proteobacteria, while α-proteobacteria may have been the primary drivers in the Symbiodiniaceae-bacterial interactions (SBIs). Our study highlights the association between microbiome shift in distinct environmental regimes and holobiont acclimatisation, while providing insights into the impact of SBIs on holobiont health and acclimatisation during climate change.