Acute lymphoblastic leukemia (ALL) is a severely invasive hematological cancer that results from the rapid increase and accumulation of lymphoid blasts in the blood, bone marrow (BM), and other organs. The pervasiveness of ALL has made it the prevalent childhood acute leukemia making up approximately 80% of leukemia in children and about 20% in adults. Due to the prevalence of ALL, more accurate diagnosis and prognostic methods are required. Proteome analysis uses a variety of analytical techniques, including protein sequencing, structural or expression proteomics, protein modification, sub-cellular protein localization, protein-protein interactions, and biological functional proteomics. Analysis of cell-signaling pathways and activation/deactivation are crucial to follow up the development, remission, or relapse of ALL. As a result, this review emphasizes cytogenetics and immunophenotyping while also highlighting the proteomic profile, clinical symptoms, diagnosis, and management of ALL. Also, it evaluates the procedures and techniques for the testing of bodily fluids (peripheral blood, cerebrospinal fluid, and BM) from ALL patients at various stages of disease, as well as the use of proteomic platforms in discovering sensitive and specific biomarkers for ALL.