Thermodynamics has long been applied in predicting undiscovered microorganisms or analyzing energy flows in microbial metabolism, as well as evaluating microbial impacts on global element distributions. However, further development and refinement in this interdisciplinary field are still needed. This work endeavors to develop a whole-cycle framework integrating thermodynamics with microbiological studies, focusing on representative nitrogen-transforming microorganisms. Three crucial concepts (reaction favorability, energy balance, and reaction directionality) are discussed in relation to nitrogen-transforming reactions. Specifically, reaction favorability, which sheds lights on understanding the diversity of nitrogen-transforming microorganisms, has also provided guidance for novel bioprocess development. Energy balance, enabling the quantitative comparison of microbial energy efficiency, unravels the competitiveness of nitrogen-transforming microorganisms under substrate-limiting conditions. Reaction directionality, revealing the niche-differentiating patterns of nitrogen-transforming microorganisms, provides a foundation for predicting biogeochemical reactions under various environmental conditions. This review highlights the need for a more comprehensive integration of thermodynamics in environmental microbiology, aiming to comprehensively understand microbial impacts on the global environment from micro to macro scales.