Different mechanisms in cancer cells become resistant to one or more chemotherapeutics is known as multidrug resistance (MDR) which hinders chemotherapy efficacy. Potential factors for MDR includes enhanced drug detoxification, decreased drug uptake, increased intracellular nucleophiles levels, enhanced repair of drug induced DNA damage, over expression of drug transporter such as P-glycoprotein(P-gp), multidrug resistance-associated proteins (MRP1,MRP2), and breast cancer resistance protein (BCRP). New chemotherapeutic drug delivery systems have been developed to combat drug resistance and multidrug resistance. Nanogel are being used to deliver drugs more effectively in cancer chemotherapy. These novel applications and techniques include: Nanogels for loading siRNA. This is a small interfering RNA (siRNA) is a class of double-stranded RNA molecules consisting of 21–23 nucleotides, involved in inhibition of protein synthesis encoded by the messenger RNAs. Nanogels are used as carriers to deliver siRNA. Another technique and application is hyaluronic acid-based nanogel-drug conjugates with enhanced anticancer activity designed for targeting of cd44-positive and drug-resistant tumors. In this technique small nanogel particles with a hydrophobic core and high drug loads formed after ultra-sonication and demonstrated a sustained drug release following the hydrolysis of biodegradable ester linkage. Other techniques and applications which will be discussed in this review article include; Novel anticancer polymeric conjugates of activated nucleoside analogs, Nanogel formulations with phosphorylated nucleoside analogs and Crosslinked Polymeric Nanogel Formulations of 5′-Triphosphates of Nucleoside analogs.