High hydrostatic pressure (HHP), as one of the main characteristics of the deep-sea environment, regulates microbial activities. However, the physiological and biochemical characteristics of microorganisms under high-pressure conditions remain largely unknown. To gain insight into the impact of HHP on deep-sea bacteria, we investigated the adaptation of three bacterial strains isolated from Pacific Ocean sediments and deep waters to different levels of HHP, including Stutzerimonas marianensis PS1 (0.1, 20, and 40 MPa), Shewanella piezotolerans WP3 (0.1, 20, and 40 MPa), and Georhizobium profundi WS11 (0.1, 30, and 60 MPa). Transcriptomic and metabolomic analyses showed that these strains adapt to HHP by modulating strain-specific metabolic reprogramming strategies and systemic resource reallocation. Specifically, the strain PS1 enhanced central carbon metabolism and unsaturated fatty acid biosynthesis to maintain energy homeostasis and membrane fluidity. The strain WP3 conserved energy by downregulating motility systems in favor of amino acid and fatty acid degradation. Conversely, the strain WS11 actively suppressed overall energy expenditure while activating glutathione metabolism to mitigate severe pressure-induced oxidative stress. Furthermore, integrated multi-omics revealed an accelerated metabolic turnover of intermediate metabolites across the strains, facilitating rapid intracellular resource redistribution. These results indicate a systemic shift in bacterial metabolic patterns regulated by HHP, further elucidating the complex physiological and biochemical adaptation mechanisms of microorganisms in the deep ocean.