Tahini (sesame paste) is a traditional food. Numerous foodborne outbreaks have been associated with it. This study aimed to (i) explore the efficiency of 2450 MHz microwave heating at 220, 330, 440, 550, and 660 W on the inactivation of Salmonella spp, Escherichia coli O157:H7, and Listeria monocytogenes in tahini; (ii) determine the impact of desiccation and starvation stresses on pathogen survival; (iii) assess the impact of microwave heating on the physicochemical characteristics of tahini. The inoculated microorganisms in tahini were reduced with higher microwave power levels (p < 0.05) and longer exposure times. The D-values of unstressed Salmonella spp., Escherichia coli O157:H7, and L. monocytogenes ranged from 6.18 to 0.50 min, 6.08 to 0.50 min, and 4.69 to 0.48 min, respectively, at power levels of 220 to 660 W, with z-values of 410, 440, and 460 W, respectively. Generally, desiccation and starvation stress levels prior to heating increased microbial resistance to heat treatment. Microwave heating did not affect acid, peroxide, p-anisidine, or color values of tahini up to 90 °C. These findings reveal microwave heating as a potential method for lowering the risk of Salmonella spp., E. coli O157:H7 and L. monocytogenes in tahini with no compromise on quality.