The evolution of nanotechnology-driven lipid and metalloid-based nanoformulations has garnered significant attention for developing effective drug delivery systems with position/time precision and efficacy. This study focuses on challenges of blood-brain barrier (BBB) and their pivotal role in drug targeting in chronic diseases such as brain tumors (BTs). These formulations encapsulate therapeutic agents within lipidic matrices, enhancing drug solubility, bioavailability, and targeted delivery. The diverse lipid materials used in these nanoformulations highlight their biocompatibility and versatility, covering a wide range of drugs. Emphasis is placed on metal nanoparticles, liposomes, ethosomes, quantum dots, carbon nanotubes, nanorobots, and micelles. The analysis explores their drug loading, stability, release characteristics, and bioavailability modulation. It also delves into the enhanced-permeability and retention (EPR) effect, crucial for passive targeting of tumors. Recent nanocarrier systems enable better penetration of therapeutic compounds through the BBB, addressing treatment failures in invasive BTs.This review highlights the latest nanotechnology developments and potential therapeutic approaches, serving as a valuable resource for researchers, clinicians, and pharmaceutical scientists.