Medication errors are associated with significant morbidity and mortality worldwide. Of various types of medication errors, administration errors are the most common. This study evaluated nurses’ knowledge of resuscitation medication administration and the obstacles they encountered while administering these medications. This multicenter, cross-sectional study was conducted among registered nurses working within public and private sector hospitals in Lahore, Pakistan. Participants were recruited using a convenient sampling technique and data were gathered using a self-completed, pre-validated questionnaire. This study included 409 nurses (age 30.09 ± 4.45 years), of whom, around 55% were found to have adequate knowledge (score > 70%) of resuscitation medications. Increasing age, experience, and hospital, and cardiovascular life support training were associated with higher knowledge scores. Furthermore, nurses from oncology, intensive care units, and emergency rooms had better knowledge (P < 0.05) than those working in other departments. Interruptions during the drug administration method (75.6%), a lack of understanding between health professionals (69.4%), and a reluctance to ask inquiries (67.7 %) were the three most common barriers encountered during the administration process. Only 55 percent of nurses had adequate knowledge, necessitating educational measures to improve nurses’ knowledge of resuscitation medications.