In the evolving landscape of toxicity assessment, the surge in demand for heightened precision and environmentally conscious methodologies has become increasingly palpable. This chapter navigates the evolving landscape of hematotoxicity and immunotoxicity assessment within the realm of drug discovery. It explores advanced methodologies surpassing the limitations of traditional methods. The journey begins with a historical overview, highlighting the transformative role of flow cytometry, and unfolds the narrative of its indispensability. Imagine a scenario without flow cytometry and delve into novel approaches-DNA methylation analysis, RNA sequencing, and multiplexed immunofluorescence-each offering unique insights into immune cell profiling and drug effects on tissues. In silico predictions, leveraging artificial intelligence, and in vitro assays, including high-throughput screening for hematotoxicity, emerge as potent tools in toxicity assessment. The exploration extends to chemico-methods, ex vivo assays, and in-depth insights into in vitro hematotoxicity assays. The abstract underscores the pivotal role of omics technologies-metabolomics, genomics, transcriptomics, and proteomics-in decoding toxicogenomics. It envisions a future where a holistic approach reshapes the assessment of hematotoxicity and immunotoxicity in drug development, aligning with the transformative potential of emerging methodologies. As tradition meets innovation, this abstract provides a glimpse into the synergy propelling drug development towards precision and efficacy. Despite significant advancements, persistent challenges such as high costs and the absence of standardized databases are underscored. The chapter concludes by emphasizing the collective impact of these diverse methodologies, pushing the boundaries of our understanding of hepatotoxic and immunotoxic phenomena in the pursuit of more effective drug development.