The objective of this study was to assess the factors associated with methamphetamine (MA) use, syphilis, and unprotected sex among female sex workers from different type of venues in Qingdao City, Shandong Province of China. Three consecutive cross-sectional surveys provided information on demographics, sexual and drug use behaviors, and HIV-related services. Of 1187 participants, 3.0% were infected with syphilis; 30.2% ever used MA; 58.3% ever had unprotected commercial sex in the past month. The prevalence rates of syphilis and MA use were 2.5% and 33.0% for participants recruited from saunas, night clubs, bars or hotels; 2.7% and 28.3% for hair/beauty salon-based participants; and 4.5% and 15.8% for street-based participants. Street-based MA users were more likely to be single, non-Shandong residents, have first lifetime sex act at younger age, and recruited in 2008 (vs. 2006). Saunas, night clubs, bars, or hotels-based MA users were more likely to be younger, sex debut at younger age, have longer duration of sex work, have unprotected commercial sex, and be syphilis-infected. Hair/beauty salon-based MA users were more likely to be non-Shandong residents, younger, and to have unprotected commercial sex. Syphilis among the sauna-, night club-, bar-, or hotel-based participants was associated with MA use and ever receipt of HIV testing. Syphilis among the hair/beauty salon-based participants was associated with longer duration of sex work. MA users who frequent commercial sex venues are engaging in high-risk behaviors and are at risk for syphilis/other sexually transmitted diseases. Better-targeted intervention efforts to curtail the epidemics of MA use and HIV/syphilis should therefore take cognizance of the role of commercial sex venues as focal points of MA use and syphilis/sexually transmitted disease transmission.