The aim of this study was to investigate an ultrasound-assisted method for the extraction of bioactive compounds from tomato pomace. This method was based on a simple ultrasound treatment using different solvents (e.g., acetone, ethanol, ethyl acetate) as extraction media. Three different variables were chosen to determine their influence on extraction efficiency, such as solvent/liquid ratio (0.1:25 g/mL, 0.2:25 g/mL, 0.3:25 g/mL), temperature (30 °C, 40 °C, 50 °C), and time (2 h, 6 h, 10 h); the variables were selected through Box–Behnken design experiments. These parameters were optimized to achieve the highest yield, and the results showed that acetone was the best extraction solvent for lycopene (3.36 mg/100 g), total phenolic content (TPC) (31.15 QUE mg/L), and total flavone content (TFC) (66.80 GAE mg/L), while DPPH activity (82.94%) was the highest when ethanol was used as the solvent. Regarding the solvent/liquid ratio, the best results were obtained at a ratio of 0.1:25. Temperature influenced the extraction, with the best results observed at 50 °C for lycopene, DPPH, and polyphenols, while the flavonoids were better extracted at 30 °C. Time played an important role as well, with the best extractions observed at 10 h. The results indicated that ultrasound-assisted extraction was suitable for extracting bioactive compounds from tomato pomace.