A total sample consumption infrared-heated system (IR-TSC) has been coupled to ICP-tandem mass spectrometry (ICP-MS/MS) for the first time. The objective of this study was to assess the analytical performance of the IR-TSC system, in terms of analytical figures of merit and mitigation of matrix effects. Twenty-seven elements have been determined: Ag, Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, K, Li, Mn, Mo, Ni, Pb, Rb, Sb, Se, Sn, Sr, Ti, Tl, V and Zn. Different operating conditions, including nebulization flow rate and spray chamber temperature, were optimized to improve sensitivity, signal stability, and plasma thermal conditions. The results showed that the infrared-heated sample introduction system improved the signal intensity by a factor of 2 to 4 compared to a conventional sample introduction system, whereas the limits of detection (LODs) improved by a factor going from 1.2 (Ba) to 3.3 (Cr) for a sample containing 2% HNO3. Meanwhile, for a 10% ethanol sample the improvement factor ranged from 1.4 (Ti) to 3.8 (Cr). Matrix effects for solutions containing inorganic acids or high content of sodium (2% HNO3, 10% HNO3, 20% HNO3, 10% HCl; 500 mg kg−1 Na, 500 mg kg−1 Na + 10% HNO3) were mitigated under optimum conditions (IR-TSC at 125 °C). Meanwhile, for solutions containing organic solvents (10% ethanol, 10% acetic acid, and 10% formic acid) it was not possible to eliminate matrix effects, even when applying an internal standard. For Se and As, elements spectrally interfered, the combination of IR-TSC sample introduction system with oxygen as reaction/collision gas mode in ICP-MS/MS provided accurate results. For 10% HNO3 and 10% HCl relative intensities values, calculated taking the signal intensity obtained for 2% HNO3 as reference, were close to the unity. Environmental and clinical control and certified reference materials were analyzed by means of an external calibration approach, with most of the elements showing concentrations not significantly different from the certified values. Finally, the IR-TSC was tested on twelve real samples, including seawater, surface water, peritoneal fluid, seminal plasma, wine, and bioethanol samples, demonstrating the system potential in different application fields.