Allogeneic hematopoietic stem cell transplantation (HSCT) and other cellular therapies are a broadly used therapeutic strategy employed against a wide range of hematological malignancies. However, these therapies are associated with significant toxicities and their efficacy is still not optimal. Our ability to study the immune system at steady state, during physiological responses and in immunopathological diseases greatly increased during the last decades thanks to the technological advances coming from different fields including cytometry, genomics and molecular imaging. In this work, we will discuss the application of these techniques to the study of the immune system after allogeneic HSCT and cellular therapies. In particular, we will see how these approaches can be applied to the understanding of new diagnostic and therapeutic strategies and exploited for their optimization. We will discuss the development of molecular imaging strategies for the immunomonitoring of T cells during GvHD. We will apply the use of multiple genomic techniques to the understanding of GvHD suppression by immune-regulatory T cells, namely regulatory T cells (Treg) and invariant natural killer T (iNKT) cells. We will study the immunomodulatory effects of engineered CAR iNKT cells on host immune-cells leading to an amplification of their antitumoral effect. We will apply high-throughput T cell receptor (TCR) sequencing to the understanding of the immunological defects during anti-SARS-CoV-2 responses in allogeneic HSCT. Finally, we will discuss the future applications of this acquired knowledge to improve the efficacy and safety of allogeneic HSCT and cellular therapies.