Nano drug delivery systems (NDDSs) have emerged as a transformative approach in cancer therapy, addressing challenges such as drug resistance, poor bioavailability, and off-target toxicity. Baicalein (BA) and baicalin (BI), flavonoids derived from Scutellaria baicalensis, exhibit potent anticancer effects but are limited by low solubility and rapid metabolism. This review classifies BA/BI-loaded NDDS into either organic or inorganic nanoparticles (NPs) and evaluates their current status, focusing on their enhanced pharmacokinetics, targeted delivery, and reduced side effects. We highlight their mechanisms of action, such as induction of apoptosis, inhibition of metastasis, and modulation of signaling pathways (e.g., PI3K/AKT, Wnt/β-catenin), across various cancers, including breast, lung, and colorectal. Preclinical studies demonstrate that BA/BI-loaded NPs significantly improve therapeutic efficacy by leveraging the enhanced permeability and retention (EPR) effect and overcoming multidrug resistance. This review synthesizes these advancements, identifies challenges in clinical translation, such as toxicity and scalability, and proposes future directions for optimizing BA/BI-based NPs for clinical application in oncology.