β-lactams have the most powerful and often administered class of antimicrobials in the health care center because of their excellent tolerance and potency. They have been used in clinical settings since 1964; cephalosporins have created significant worldwide burdens that make the bacteria develop resistance. Bacterial resistance to antibiotics could be innate or acquired resistance and classified into four types according to mechanisms, target site modification, change in membrane permeability, forced efflux from the cytosol and antibiotic inactivation. Cephalosporin resistance has developed worldwide, creating a serious risk to its continued use so it’s very important to develop strategies to restore and maximize the performance of this important class of antibiotics such as cephalosporin derivatives, β-lactamase inhibitors, prodrugs, acting with intracellular bacteria and the use of drug nano-carriers. Among the most productive strategies to increase the performance of β-lactams is to use nanocarriers such as nanoparticles, liposomes, and niosomes. Nanocarriers may improve β-lactamases activity in the long run by minimizing resistance to antimicrobials and assisting in delivering the medicine to the target sites. The particle's surfaces are then modified using a particular type of surface active agent to allow medication release control and could be linked to antibodies or other recognition components allow recognition of a specific cellular target.