The complex interplay between solute carrier (SLC) transporters and noncoding RNAs (ncRNAs) in regulating genetic and metabolic pathways in hematological disorders remains underexplored. This chapter addresses the critical need to understand how these regulators influence the development, progression, and therapeutic resistance of leukemia. By elucidating these mechanisms, this chapter aims to contribute to the development of novel, targeted interventions for improved clinical outcomes. This chapter delves into the multifaceted roles of SLC transporters and ncRNAs in blood cell regulation, highlighting their impact on hematopoiesis and leukemogenesis. Topics include the hierarchical differentiation of hematopoietic stem cells, the molecular subtypes of leukemia, and the regulatory roles of transcription factors and chromatin modifiers in leukemia progression. Additionally, this chapter explores how SLC transporters mediate nutrient uptake, drug resistance, and metabolic adaptations in leukemic cells. It further examines the involvement of ncRNAs—such as microRNAs, long noncoding RNAs, and circular RNAs—in modulating transporter activity, impacting both normal and malignant hematopoietic processes. Through these discussions, this chapter offers critical insights into the therapeutic potential of targeting SLC transporters and ncRNAs in leukemia treatment. It underscores the importance of understanding the genetic and epigenetic landscapes of blood disorders to develop precision medicine approaches. By integrating recent advancements and highlighting gaps in knowledge, this chapter provides a foundation for future research aimed at overcoming the challenges of multidrug resistance and enhancing treatment efficacy in hematological malignancies.