In recent studies, lipid nanoparticles have attracted attention as drug delivery systems owing to their preeminent potential in achieving the desired bioavailability of biopharmaceutics (BCS) class II and class IV drugs. The current debate concerns the bioavailability of these poorly absorbed drugs with their simultaneous oral degradation. Lipid nanoparticles, including solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), are lipid-based carrier systems that can effectively encapsulate both lipophilic and hydrophilic drugs, offering versatile drug delivery systems. The unique properties of lipids (biodegradability and biocompatibility) and their transportation pathways enhance the biological availability of drugs. These particles can increase the gastrointestinal absorption and solubilization of minimally bioavailable drugs via a selective lymphatic pathway. This review mainly focuses on providing a brief update on lipid nanoparticles (LNPs) that synergistically increase the bioavailability of limited permeable drugs and highlight the transversal mechanisms of LNPs across the gastrointestinal hurdles, transmembrane absorption, transport kinetics, and computational tools. Finally, the present hurdles and future perspectives of LNPs for oral drug delivery systems are discussed.