Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 health emergency, affecting and killing millions of people worldwide. Following SARS-CoV-2 infection, COVID-19 patients show a spectrum of symptoms ranging from asymptomatic to very severe manifestations. In particular, bronchial and pulmonary cells, involved at the initial stage, trigger a hyper-inflammation phase, damaging a wide range of organs, including the heart, brain, liver, intestine and kidney. Due to the urgent need for solutions to limit the virus’ spread, most efforts were initially devoted to mapping outbreak trajectories and variant emergence, as well as to the rapid search for effective therapeutic strategies. Samples collected from hospitalized or dead COVID-19 patients from the early stages of pandemic have been analyzed over time, and to date they still represent an invaluable source of information to shed light on the molecular mechanisms underlying the organ/tissue damage, the knowledge of which could offer new opportunities for diagnostics and therapeutic designs. For these purposes, in combination with clinical data, omics profiles and network models play a key role providing a holistic view of the pathways, processes and functions most affected by viral infection. In fact, in addition to epidemiological purposes, networks are being increasingly adopted for the integration of multiomics data, and recently their use has expanded to the identification of drug targets or the repositioning of existing drugs. These topics will be covered here by exploring the landscape of SARS-CoV-2 survey-based studies using systems biology approaches derived from omics data, paying particular attention to those that have considered samples of human origin.