Effective cancer therapy is daunted with challenges such as limited drug concentration at the target site, non-specific drug distribution, rapid clearance, and drug resistance. A smart approach to overcome most of these challenges is through targeting drugs to tumors. The tumor microenvironment (TME) offers unique features like acidosis, hypoxia, elevated reactive oxygen species (ROS), and glutathione (GSH), which can be harnessed for site-specific targeted drug delivery. Stimuli-responsive nanosystems exploit these endogenous conditions (pH, enzymes, redox imbalance) or rely on exogenous triggers (ultrasound, temperature, magnetic fields) to achieve precise, controlled drug release. Endogenous stimuli-responsive systems leverage TME-specific conditions for selective drug activation, while external triggers enable spatiotemporal control via physical energy sources. This chapter discusses recent advances in smart nanocarriers, detailing their mechanism of action and the therapeutic benefits they offer. Stimuli-responsive nanosystems enhance tumor targeting, reduce off-target effects, and improve treatment efficacy. The chapter provides an overview of the design and application of these advanced delivery platforms, highlighting their potential to overcome limitations in conventional cancer therapy, and serves as a prelude to the book, which is a detailed coverage of stimuli-responsive nanosystems.