The article reviews the application of electrospun drug-loaded nanofibers in cancer therapy, highlighting their potential to address the challenges of chemotherapy, such as drug resistance and systemic side effects. Electrospinning is a technique that creates nanofibers by energizing polymer droplets, allowing for sustained and controlled drug release. The core–sheath structure in electrospun fibers enables the loading of multiple drugs, facilitating synergistic treatment and minimizing patient discomfort. These fibers can also integrate metal particles and targeted compounds, enabling combinations of chemotherapy with magnetic and heat therapies. The review covers various aspects of electrospinning, including preparation techniques and drug delivery methods tailored to different cancers. Single-fluid, double-fluid, and multi-fluid electrospinning are discussed, each with its advantages and applications. Single-fluid electrospinning produces smooth and continuous fibers, while double-fluid electrospinning creates core–sheath structures, and multi-fluid electrospinning allows for precise control over fiber attributes. The article also explores different drug release modes, such as rapid, sustained, biphasic, targeted, and combined release, each with specific therapeutic benefits. For example, rapid release is useful for addressing pain and fever, while sustained release is effective for chronic conditions like cancer. Biphasic release combines rapid and sustained release, and targeted release uses pH-sensitive materials to target specific organs or tissues. The application of drug-loaded nanofibers in cancer therapy is detailed across various types of cancer, including breast, skin, cervical, colon, lung, brain, and oral cancers. Each section highlights the unique challenges and solutions in cancer treatment, such as the use of magnetic nanoparticles, temperature-responsive fibers, and pH-sensitive materials. The review emphasizes the high drug loading, encapsulation efficiency, and specific drug release profiles of electrospun nanofibers, making them promising tools for localized and effective cancer treatment.The article reviews the application of electrospun drug-loaded nanofibers in cancer therapy, highlighting their potential to address the challenges of chemotherapy, such as drug resistance and systemic side effects. Electrospinning is a technique that creates nanofibers by energizing polymer droplets, allowing for sustained and controlled drug release. The core–sheath structure in electrospun fibers enables the loading of multiple drugs, facilitating synergistic treatment and minimizing patient discomfort. These fibers can also integrate metal particles and targeted compounds, enabling combinations of chemotherapy with magnetic and heat therapies. The review covers various aspects of electrospinning, including preparation techniques and drug delivery methods tailored to different cancers. Single-fluid, double-fluid, and multi-fluid electrospinning are discussed, each with its advantages and applications. Single-fluid electrospinning produces smooth and continuous fibers, while double-fluid electrospinning creates core–sheath structures, and multi-fluid electrospinning allows for precise control over fiber attributes. The article also explores different drug release modes, such as rapid, sustained, biphasic, targeted, and combined release, each with specific therapeutic benefits. For example, rapid release is useful for addressing pain and fever, while sustained release is effective for chronic conditions like cancer. Biphasic release combines rapid and sustained release, and targeted release uses pH-sensitive materials to target specific organs or tissues. The application of drug-loaded nanofibers in cancer therapy is detailed across various types of cancer, including breast, skin, cervical, colon, lung, brain, and oral cancers. Each section highlights the unique challenges and solutions in cancer treatment, such as the use of magnetic nanoparticles, temperature-responsive fibers, and pH-sensitive materials. The review emphasizes the high drug loading, encapsulation efficiency, and specific drug release profiles of electrospun nanofibers, making them promising tools for localized and effective cancer treatment.