This review provides an in-depth overview of stimulus-responsive hydrogels for targeted cancer therapy. Hydrogels, due to their high water content, adjustable mechanical properties, and responsiveness to various stimuli, are promising nanocarriers for controlled drug delivery within the tumor microenvironment (TME). The TME, characterized by acidic pH, hypoxia, and elevated enzyme levels, presents significant challenges for conventional cancer treatments. Stimulus-responsive hydrogels can be designed to release therapeutic agents in response to specific stimuli such as pH, temperature, light, and enzymes, enhancing treatment efficacy while minimizing side effects. The review covers various types of stimuli-responsive hydrogels, including pH-responsive, redox-responsive, enzyme-responsive, and glucose-responsive hydrogels. Each type is discussed in detail, highlighting their mechanisms of action, synthesis methods, and applications in cancer therapy. For example, pH-responsive hydrogels can be tailored to release drugs in acidic environments, while redox-responsive hydrogels can respond to changes in the redox state of the environment. Enzyme-responsive hydrogels can target sites with elevated enzyme levels, and glucose-responsive hydrogels can deliver insulin for diabetes management. Physical stimuli-responsive hydrogels, such as thermo-responsive and light-responsive hydrogels, are also explored. Thermo-responsive hydrogels undergo a sol-gel transition in response to temperature changes, allowing for controlled drug release. Light-responsive hydrogels use light-sensitive moieties to trigger reversible structural changes, enabling precise control over drug release. The review concludes by discussing the potential of multi-stimuli-responsive hydrogels, which can respond to multiple stimuli simultaneously, offering enhanced flexibility and precision in cancer treatment. Overall, the advancements in stimulus-responsive hydrogels represent a significant step forward in the development of targeted and effective cancer therapies.This review provides an in-depth overview of stimulus-responsive hydrogels for targeted cancer therapy. Hydrogels, due to their high water content, adjustable mechanical properties, and responsiveness to various stimuli, are promising nanocarriers for controlled drug delivery within the tumor microenvironment (TME). The TME, characterized by acidic pH, hypoxia, and elevated enzyme levels, presents significant challenges for conventional cancer treatments. Stimulus-responsive hydrogels can be designed to release therapeutic agents in response to specific stimuli such as pH, temperature, light, and enzymes, enhancing treatment efficacy while minimizing side effects. The review covers various types of stimuli-responsive hydrogels, including pH-responsive, redox-responsive, enzyme-responsive, and glucose-responsive hydrogels. Each type is discussed in detail, highlighting their mechanisms of action, synthesis methods, and applications in cancer therapy. For example, pH-responsive hydrogels can be tailored to release drugs in acidic environments, while redox-responsive hydrogels can respond to changes in the redox state of the environment. Enzyme-responsive hydrogels can target sites with elevated enzyme levels, and glucose-responsive hydrogels can deliver insulin for diabetes management. Physical stimuli-responsive hydrogels, such as thermo-responsive and light-responsive hydrogels, are also explored. Thermo-responsive hydrogels undergo a sol-gel transition in response to temperature changes, allowing for controlled drug release. Light-responsive hydrogels use light-sensitive moieties to trigger reversible structural changes, enabling precise control over drug release. The review concludes by discussing the potential of multi-stimuli-responsive hydrogels, which can respond to multiple stimuli simultaneously, offering enhanced flexibility and precision in cancer treatment. Overall, the advancements in stimulus-responsive hydrogels represent a significant step forward in the development of targeted and effective cancer therapies.