Purpose: We present a case of fatal intoxication with U-47700 in combination with other NPS (N-ethylhexedrone, adinazolam, 4-chloro-N-isopropylcathinone (4-CIC), 4-chloromethcathinone (4-CMC) and sertraline) confirmed by identification and quantification in biological materials and evidences found at the scene in 2017 in Poland. Methods: Blood and urine samples were extracted with ethyl acetate from alkaline medium (pH 9); powders/crystals were diluted with methanol. The analysis was carried out using ultra-high-performance liquid chromatography–tandem mass spectrometry. Validation criteria were evaluated for blood and urine at the concentrations of 10 and 100 ng/mL. Results: The validation parameters of the method were within acceptable ranges. In the presented case, the determined concentrations of drugs were as follows, in blood: U-47700, 1470 ng/mL; N-ethylhexedrone, 58 ng/mL; adinazolam, 18 ng/mL; 4-CIC, 8.0 ng/mL; 4-CMC, 1.7 ng/mL; in urine: U-47700, 3940 ng/mL; N-ethylhexedrone, 147 ng/mL; adinazolam, 82 ng/mL; 4-CIC, 130 ng/mL; 4-CMC, 417 ng/mL. Sertraline (blood, 89 ng/mL; urine, 32 ng/mL) was also determined in both materials. The same substances were also found in 5 powders/crystals: U-47700 (12% by weight), N-ethylhexedrone (54%), adinazolam (14%), 4-CIC (23%), 4-CMC (26%). After 775 days of storage, biological samples at + 4 °C, the most stable substance was sertraline and the less, synthetic cathinones, especially 4-CIC and 4-CMC. Conclusions: The described case of fatal intoxication with NPS presented postmortem concentrations of U-47700, 4-CMC, N-ethylhexedrone, adinazolam and 4-CIC for the first time in the literature. The paper also showed stability study of these substances stored at + 4 °C for 775 days.