Background: Pre-exposure prophylaxis (PrEP) is a valuable tool in the response to the HIV epidemic, recommended for groups with a higher risk of HIV infection, such as men who have sex with men (MSM), particularly in the context of high-risk sexual behavior such as chemsex. Purpose: This study aimed to analyze the prevalence and factors associated with the intention to use PrEP among MSM who engage in chemsex in Brazil and Portugal. Methods: This was a cross-sectional study of a secondary dataset from a larger study conducted between January 2020 and May 2021 throughout Brazil and Portugal involving 1852 MSM who engage in chemsex. An initial descriptive analysis was performed to calculate the absolute and relative frequencies of independent variables related to the intention to use PrEP among MSM. A multivariate regression model was developed to identify factors independently associated with the intention to use PrEP. Results: Although a high level of PrEP knowledge (85.75%) was observed among MSM who engage in chemsex, the prevalence of intention to use PrEP was only 59.07%. Five variables were associated with a higher prevalence of intention to use PrEP [engaging in double penetration – adjusted prevalence ratio (aPR): 1.56, 95% CI: 1.44–1.69; being assigned female sex at birth – aPR: 1.34, 95% CI: 1.12–1.61; cruising – aPR: 1.21, 95% CI: 1.06–1.38; not using condoms – aPR: 1.20, 95% CI: 1.05–1.36; and being an immigrant – aPR: 1.16; 95% CI: 1.07–1.25], while having knowledge of postexposure prophylaxis (aPR: 0.91; 95% CI: 0.84–0.98), having a casual sexual partner (aPR: 0.86 and 0.85; 95% CI: 0.74–0.99 and 0.74–0.98), and engaging in group sex (aPR: 0.81; 95% CI: 0.73–0.90) were associated with a lower intention to use PrEP. Conclusion: The intention to use PrEP among MSM who engage in chemsex was high, and several factors were associated with this intention. Understanding the factors associated with the intention to use PrEP among MSM practicing chemsex is crucial for developing targeted interventions to increase PrEP uptake in this population. The results of this study suggest that tailored approaches are necessary to promote PrEP use in this population.