Heme proteins mediate a medley of pivotal transformations in a humans, which include various oxidation, oxygenation, nitration, nitrosation, and other types of organic transformation reactions among others. Accordingly, these pathways have remained to be of prime interest in designing effective therapeutic agents against an array of challenging disease situations. To this end, mechanistic details of these key enzymes have been a focal point of research, nonetheless, many key features still remain enigmatic to-date. In particular, mechanisms of heme enzyme pathways driven by mid-valent intermediates (i.e., Fe(III)-containing) such as superoxo, peroxo, hydroperoxo, peroxynitrito, hyponitrito etc. have been historically understudied. However, such reaction intermediates are becoming progressively more relevant in therapeutically pivotal mechanisms, mandating a comprehensive understanding of basic structural and functional attributes. We utilize synthetic model systems to address this key deficit, wherein precise structural alterations are relatively more straightforward compared to their biological counterparts. We have utilized a series of electronically divergent heme model compounds along with various bioinspired axial ligands (i.e., mimicking proximal ligand of heme active sites) to shed light on important reactivity properties of heme peroxo and heme nitrosyl adducts. The former is primarily nucleophilic and has been proposed to mediate the second mechanistic step of the main arginine degrading (aerobic) heme enzyme, nitric oxide synthase (NOS), where the axial ligand plays a key role in dictating reactivity, especially via modulating nucleophilicity. Heme ferrous nitrosyls are typically inert; however, we observe that their reactivity toward dioxygen can be ‘turned on’ when axially ligating thiolates are present, mimicking the futile cycle of NOS. In detail descriptions into geometric and electronic structures of these axially ligated mid-valent heme intermediates will be discussed in detail, shedding light on how those structural properties in turn modulate their biologically important reactivity properties, especially in relevance to those that are implicated in pathogenic situations.