Electrospun chitosan drug delivery systems (DDS) carry great fortune to the next era of therapeutic technologies and biomedical applications. These systems have been successfully applied to a wide range of biomedical and therapeutic applications due to their unique advantages and biocompatible characteristics. Advanced DDS are rapidly revolutionizing in the modern era of therapeutics, to fill the gaps and drawbacks associated with conventional pharmaceutical formulations. Advanced DDS are techniques or devices fabricated to deliver therapeutic materials to target diseased body sites, increasing treatment efficacy and safety by regulating formulation properties (e.g., release rate, timing, targeting to tissue). Advanced DDS aim to enhance pharmacological efficacy, balancing challenges associated with traditional pharmaceuticals such as low/inconsistent solubility, permeability, and bioavailability, while decreasing toxicity and adverse drug reactions (ADRs). Electrospinning allows the fabrication of continuous polymer fibers, within the micrometer or nanometer scale, by exposing a polymer solution or melt to high voltages. Electrospinning is a very effective technique used to fabricate chitosan nanofibers. Electrospinning shows high versatility; it allows incorporating a wide range of therapeutic agents, including low solubility drugs, proteins, and DNA, and allows sustained and controlled-release designs. Chitosan is a non-toxic, naturally occurring biopolymer that exhibits unique characteristics that are useful for numerous applications, such as advanced DDS and biomedical technologies (e.g., tissue engineering and tissue regeneration). Inherently, it possesses antimicrobial, antioxidant, anticancer, non-toxic, biocompatible, and biodegradable properties. Combining electrospinning methods with chitosan results in advanced DDS with synergistic performance by utilizing the unique properties of both. Electrospun-based chitosan fibers are used in advanced DDS due to several advantageous characteristics, such as optimized porosity, mechanical characteristics, boosted surface functionality, vast surface area, and pore size distribution across various scales. Functionalized electrospun chitosan-based nanofibers are modernly utilized to produce top-notch DDS and boosted scaffolds for the new era of medicine, such as regenerative medical applications, wound treatment, targeted drug therapy, personalized medicine, and antimicrobial coatings. As a result of their multifunctionality, biocompatibility, and capacity for controlled release, chitosan-based electrospun DDS represent an up-and-coming platform for diverse therapeutic and biomedical applications. This chapter discusses the characteristics, production, revolution, advancements, application, limitations, and challenges of electrospun chitosan advanced DDS. This chapter aims to comprehensively analyze chitosan-based electrospun DDS, focusing on their fabrication techniques, critical process parameters, properties, and biomedical applications in targeted and sustained therapeutics. Associated drug release and delivery mechanisms are explained. Applications of electrospun chitosan in drug delivery, including wound dressings, tissue engineering, bone regeneration, other diseases, and biomedical applications are explained in depth and suggested strategic solutions and future perspectives are proposed.