The COVID-19 pandemic has had a significant impact on global mortality. While the causal relationship between SARS-CoV-2 and the anomalous increase in deaths is established, more precise and complex models are needed to determine the exact weight of epidemiological factors involved. Indeed, COVID-19 behavior is influenced by a wide range of variables, including demographic characteristics, population habits and behavior, healthcare performance, and environmental and seasonal risk factors. The bidirectional causality between impacted and impacting aspects, as well as confounding variables, complicates efforts to draw clear, generalizable conclusions regarding the effectiveness and cost-benefit ratio of non-pharmaceutical health countermeasures. Thus, it is imperative that the scientific community and health authorities worldwide develop comprehensive models not only for the current pandemic but also for future health crises. These models should be implemented locally to account for micro-differences in epidemiological characteristics that may have relevant effects. It is important to note that the lack of a universal model does not imply that local decisions have been unjustified, and the request to decrease scientific uncertainty does not mean denying the evidence of the effectiveness of the countermeasures adopted. Therefore, this paper must not be exploited to denigrate either the scientific community or the health authorities.