Abstract Upon its discovery in 2020 March, we requested Director Discretionary Time (DDT) at the NASA/IRTF facility to observe comet C/2020 F3 (NEOWISE), with the high-resolution spectrograph iSHELL. The comet approached the Sun, down to 0.3 au, in early 2020 July, providing a spectacular perihelion passage and revealing itself as one of the brightest comets that have appeared in the northern hemisphere in recent decades. Daytime observations with iSHELL/IRTF were performed to study the comet immediately after its perihelion passage, from 9 July to 1 August. In early August, a DDT at Keck Observatory was requested to continue following the comet with NIRSPEC 2.0. We acquired comprehensive high-resolution spectra of the comet as it progressively retreated from perihelion. We detected many cometary emission lines in the (2.8–5.3) μm range, identifying 12 molecular species: 9 primary volatiles (H₂O, HCN, NH₃, CO, C₂H₂, C₂H₆, CH₄, CH₃OH, and H₂CO) and 3 product species (CN, NH₂, OH). In this paper, we present the analysis and discussion of the molecular abundances found in this comet, and we compare them to reference median values for Oort Cloud Comets. Measured molecular mixing ratios showed drastic changes during our observing campaign, which spanned nearly one month from 2020 July 9 to August 6. Here, we provide a detailed discussion of the molecular spatial distributions and their role in identifying the presence of extended sources in the coma. Our investigations provided evidence for the heterogeneous chemical composition of the comet’s nucleus.