Purpose: Inflammation and neutrophils play a central role in both Covid-19 disease and cancer. We aimed to assess the impact of pre-existing tumor-related inflammation on Covid-19 outcomes in patients with cancer and to elucidate the role of circulating neutrophil subpopulations. Methods: We conducted a multicenter retrospective analysis of 524 patients with cancer and SARS-CoV-2 infection, assessing the relationship between clinical outcomes and circulating inflammatory biomarkers collected before and during Covid-19 infection. Additionally, a unicenter prospective cohort provided data for an exploratory analysis, assessing the immunophenotype of circulating neutrophils and inflammatory cytokines. The primary endpoints were 30-day mortality and severity of Covid-19 disease. Results: Prior to Covid-19, 25% of patients with cancer exhibited elevated dNLR, which increase to 55% at the time of Covid-19 diagnosis. We developed the FLARE score, incorporating both tumor and infection-induced inflammation, which categorized patients into four prognostic groups. The poor prognostic group had a 30-day mortality rate of 68%, significantly higher than the 23% in the favorable group (p<0.0001). The score proved to be an independent predictor of early mortality. The prospective analysis revealed a shift towards immature forms of neutrophils and higher IL-6 levels in patients with cancer and severe Covid-19 infection. Conclusions: A pre-existing tumor-induced pro-inflammatory state significantly impacts Covid-19 outcomes in patients with cancer. The FLARE score serves as an easy-to-use and worldwide accessible effective tool to predict outcomes in this population, while circulating neutrophil subpopulations might provide additional information and could help refine outcome prediction.