Data in this article provides detailed information on the microbial dynamics and degradation performances in two full-scale anaerobic digesters operated in parallel for 476 days. One of them was kept at 35 °C for the whole experiment, while the other was submitted to sub-mesophilic (25 °C) conditions between days 123 and 373. Sludge samples were collected from both digesters at days 0, 80, 177, 218, 281, 353, and 462. The provided data include the operational conditions of the digesters and the characterization of the sludge samples at the physicochemical level, indicative of the digesters’ degradation performance. It also includes the characterization of the sludge samples at the multiomics level (16S rRNA gene sequencing, metagenomics, and metabolomics profiling), to decipher the changes in the microbial structure and molecular activity. The 16S rDNA gene sequencing, metagenomics, and metabolomics data were generated using an IonTorrent PGM sequencer, an Illumina NextSeq 500 sequencer, and LTQ-Orbitrap XL mass spectrometer respectively. The 16S rDNA gene raw data and the metagenomics data have been deposited in the BioProject PRJEB49115, in the ENA database (https://www.ebi.ac.uk/ena/browser/view/PRJEB49115). The metabolomics data has been deposited at the Metabolomics Workbench, with study id ST002004 (DOI: 10.21228/M8JM6B). The data can be used as a source for comparisons with other studies working with data from full-scale anaerobic digesters, especially for those investigating the effect of the temperature modification. The data is associated with the research article “Metataxonomics, metagenomics, and metabolomics analysis of the influence of temperature modification in full-scale anaerobic digesters” (Puig-Castellví et al ).