MDM2 and hydrops fetalis: This review provides a significant update by synthesizing the most recent discoveries of HF’s mechanisms (e.g., MDM2-p53 axis, casein kinase 2 (CK2) inhibition) and distinctly focuses on critically analyzing controversial pharmacological data, providing an in-depth discussion of pharmacokinetic challenges and advanced nano-formulation strategies, and offering a forward-looking perspective on translational barriers—aspects not comprehensively covered in earlier works.