Cigarette smoke (CS) exposes users to harmful substances, contributing to chronic lung diseases. Heated tobacco products (HTPs) are marketed as safer alternatives due to their lower toxicant emissions from heating rather than burning tobacco. However, HTPs may produce unique toxicants that are not found in CS. The emissions of carbonyls and tobacco-specific nitrosamines (TSNAs) were compared using targeted analysis using liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UPLC-MS/MS) and untargeted analysis with UPLC-QToF and Progenesis® QI software. Targeted analysis revealed that HTP aerosol emissions contain significantly lower levels of harmful compounds compared to CS, with reductions of 8.7% to 91.6% in 11 carbonyls and 85.7% to 95.4% in four TSNAs) Untargeted analysis identified 25 carbonyls and seven nitrosamines in both HTPs and conventional cigarettes, with acetoin, dimethylbenzaldehyde, furfural, and diisopropanolnitrosamine (DIPN) found at relatively high levels in HTPs. While untargeted methods introduce some uncertainty, these findings underscore distinct chemical differences between HTPs and conventional cigarettes. Long-term studies are essential to fully understand the health implications of HTP use.