The role of immune signaling networks in immunometabolism is emerging as a promising area of research, which could provide a valuable tool to redesign therapeutic options to contain allograft rejection and the progression of chronic fibrosis. Here, we have discussed the critical roles of T cell's energy generation, roles in immunomodulation, and the impact of immunomodulation on transplantation. Altogether, the power of these metabolic signals contributes to the differentiation of Teffs; therefore, our understanding of the metabolic disparity among T-cell populations would open up new avenues to design therapeutic strategies to prevent inflammatory-related diseases.