Multifunctional drug delivery systems incorporating 5-fluorouracil (5-FU) represent a novel therapeutic strategy in cancer target treatment while minimizing damage to healthy cells. This study aimed to develop and evaluate new hydrogel compositions based on poly(vinylpyrrolidone), carboxymethylcellulose, poly(ethylene glycol), and agar, synthesized and sterilized via e-beam irradiation using a dose of 30 kGy. The cross-linked hydrogels were evaluated in terms of swelling properties in different pH media from 4 to 8, mechanical properties, drug loading capacity, and in vitro drug release and biodegradation profiles. Additionally, the 5-FU release kinetics was investigated using several mathematical models. The swelling results showed that the pH of the solutions had a substantial impact on swelling, as well as on drug loading capacity. Compared to the basic medium (970%), a greater absorption capacity was seen at pH 7.4 (1385%) and in an acidic medium (1200%). In comparison to the loss modulus (G" = 1580 Pa), the hydrogels showed noticeably higher storage modulus values (G' = 36,700 Pa), indicating elastic behavior and confirming the existence of a stable macromolecular network. Notably, this hydrogel demonstrates a higher 5-FU drug-loading capacity of 5.5 mg/g at pH 6, exhibiting a cumulative release profile of 96% at pH 5 and 80% at pH 7.4 within 30 hours. The experimental kinetic data fit best to the Korsmeyer–Peppas, Peppas–Sahilin, and Makoid–Banakar kinetics models with correlation coefficients (r²) above 0.99, revealing a Fickian mechanism transport of 5-FU within the hydrogel matrix. The aforementioned findings show that hydrogel has the potential to be used as an intelligent wound dressing for the treatment of local cancer.