<p>Cancer continues to remain a global health challenge, and conventional chemotherapy has its own limitations such as poor solubility, systemic toxicity, nonspecific biodistribution, and multidrug resistance (MDR). Nanostructured Lipid Carriers<b> (</b>NLCs) have proved as one of the effective drug delivery systems which can overcome all challenges of conventional technologies by enhancing therapeutic efficacy with reduced side effects. Therefore, this comprehensive review describes, in detail the structure, composition, formulation characteristics of NLCs, and manufacturing techniques. NLCs have shown significant advantages including enhanced drug solubility, controlled release characteristics, and encapsulation of hydrophilic as well as lipophilic drugs. Passive and active targeting enables NLCs to maximize the accumulation of drugs at targeted tumor sites through the enhanced permeation retention (EPR) effect. In addition, MDR targeting and long-circulating NLCs can enhance effectiveness against the resistance mechanisms of cancer cells. Cancer theranostics integrated with NLCs provide real-time diagnosis and treatment opportunities. Despite all these potential advantages, NLCs are still facing a few challenges of large-scale manufacturing, toxicity issues, and regulatory approvals. Yet, recent progress in personalized medicine and lipid-based nanotechnology reflects the potential of NLCs as a versatile and efficient delivery system for anticancer drugs. This review tries to clarify the evolving aspect of NLCs as well as the challenges faced in cancer treatment and strategies to overcome them by focusing on their ability to reshape chemotherapy and improve patient compliance.</p> Graphical Abstract <p></p>