Background: Rising cannabis use poses significant challenges in the administration of general anesthetics, particularly propofol, due to potential alterations in pharmacodynamics caused by tetrahydrocannabinol and its interactions with central nervous system receptors. This systematic review and meta-analysis aims to consolidate the existing literature to quantify propofol requirements in cannabis users, highlighting the complex relationship between cannabis use and anesthetic management. Methods: A systematic search of English-language literature was conducted to identify studies with data on propofol dosing in adult cannabis users. Propofol requirements were defined as the total intraoperative dose needed to achieve and maintain adequate sedation or anesthesia, assessed using parameters like monitoring and procedural tolerance. A random-effects model was used with DerSimonian–Laird estimations for pooled effect sizes and 95% confidence intervals. Heterogeneity was assessed using I2 and Cochran’s Q statistics, and sensitivity analysis was conducted by grouping publications by design, size, and quality. Results: Eight qualified studies were identified with 2268 patients included. Patients who used cannabis were typically younger and more likely to smoke tobacco than non-users. Propofol requirements were significantly higher in cannabis users, who required an average additional dose of 47.33 mg compared to non-users. Subgroup analyses revealed that cannabis users undergoing general anesthesia needed an additional 30.57 mg intraoperatively, while those undergoing sedation for endoscopic procedures required an additional 53.02 mg. Conclusions: These results underscore the need for personalized anesthetic plans to accommodate physiological variations in cannabis users. However, the lack of standardized definitions for propofol requirements and the heterogeneity across studies necessitate caution in interpretation. The observed increase in propofol requirements suggests altered central nervous system sensitivities and receptor changes in cannabis users, emphasizing the need for further research to establish clear definitions, elucidate underlying mechanisms, and refine clinical guidelines for anesthetic management in this population.