Data-driven approaches were applied to investigate the temporal and spatial changes of 1,022 individuals of wild yellowfin goby and its potential interaction with the estuarine environment in Japan. Nuclear magnetic resonance (NMR)-based metabolomics revealed that growth stage is a primary factor affecting muscle metabolism. Then, the metabolic, elemental and microbial profiles of the pooled samples generated according to either the same habitat or sampling season as well as the river water and sediment samples from their habitats were measured using NMR spectra, inductively coupled plasma optical emission spectrometry and next-generation 16 S rRNA gene sequencing. Hidden interactions in the integrated datasets such as the potential role of intestinal bacteria in the control of spawning migration, essential amino acids and fatty acids synthesis in wild yellowfin goby were further extracted using correlation clustering and market basket analysis-generated networks. Importantly, our systematic analysis of both the seasonal and latitudinal variations in metabolome, ionome and microbiome of wild yellowfin goby pointed out that the environmental factors such as the temperature play important roles in regulating the body homeostasis of wild fish.