Community pharmacists are the most accessible healthcare professionals. Recently, the increasing trend of tramadol and gabapentinoids prescription has become a global problem, with a high risk of misuse and abuse. This study mainly assessed the knowledge and practice of Lebanese pharmacists regarding the use of gabapentinoids and tramadol, and also identified the predictors of knowledge. A cross-sectional survey was conducted on a sample of 295 Lebanese community pharmacists over a period of 4 months. Data were collected using a questionnaire filled online by the participants. Knowledge scores for tramadol and gabapentinoids together and for each separately were computed and dichotomized into poor and good knowledge. Data were analyzed using SPSS version 22 (SPSS Inc., Chicago, IL, USA). The mean scores of tramadol and gabapentinoids knowledge individually were 18 ± 7 and 18 ± 6, respectively; 52.9% and 52.5% had good knowledge, whereas 47.1% and 47.5% had poor knowledge concerning these drugs, respectively. Moreover, it was observed that having a master's degree increases knowledge about tramadol and gabapentinoids by approximately two times. Regarding pharmacists' practice concerning tramadol and gabapentinoids dispensing, 97.6% and 71.5% of pharmacists, respectively, do not dispense them without prescription. About 43% of pharmacists believe that current governmental regulations are not adequate to control the problem of misuse, with 86.8% citing the need for new laws and better supervision on such drugs to limit their misuse. This study highlighted that pharmacists' knowledge concerning tramadol and gabapentinoids needs to be improved, reflecting the importance of enrolling pharmacists in continuous learning system.