In the evolving landscape of cancer research, the identification of key molecular players that contribute to the disease's progression and resistance against treatments has become paramount. Among these, Maternal Embryonic Leucine Zipper Kinase (MELK) has emerged as a critical regulator of cancer cell proliferation, survival, and therapy evasion. Concurrently, the significance of non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in modulating gene expression and cancer phenotypes has been increasingly recognized. Given the pivotal roles both MELK and ncRNAs play within cancer biology, investigating their interactions presents a compelling new frontier for therapeutic innovation. This exploration not only promises to enhance our understanding of cancer's molecular underpinnings but also opens up avenues for developing novel targeted interventions. The rationale behind focusing on MELK-ncRNA crosstalk lies in the potential to disrupt these critical molecular interactions, thereby offering a novel strategy to counteract cancer progression and improve treatment outcomes.