The application of chimeric antigen receptor T cell (CAR-T) immunotherapy has ushered in a new era in cancer therapy, especially in the treatment of many kinds of refractory malignant tumors. The curative effect is significant for refractory/recurrent hematologic malignancies, such as acute leukemia, lymphoma, and multiple myeloma (MM). Tumor microenvironment (TME) is closely related to the efficacy and adverse reactions of CAR-T therapy. TME not only affects the activity of CAR-T cells, reduces their anti-tumor ability, but also directly involved in the occurrence and development of CAR-T cell therapy-related adverse reactions, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Therefore, a deeper understanding of the role of blood TME in the process of CAR-T immunotherapy and the occurrence and development of adverse reactions is helpful for the application of CAR-T therapy in hematological malignancies. In this review, the influence of blood TME on the efficacy and adverse reactions of CAR-T immunotherapy was briefly summarized, aiming to provide evidence-based support for the clinical optimization of therapeutic regimen of refractory/recurrent hematologic malignancies.