Background: Tobacco consumption is a major public health threat with significant implications. This study aimed to assess the prevalence of tobacco abuse and five tobacco-related cancers (lung, bladder, colorectal, stomach, and other digestive cancers) across the five Regional Health Administrations (RHA) of mainland Portugal in 2021–2023. It also investigated three key indicators related to smoking habits and cessation, with a secondary ongoing objective of exploring associations between tobacco use, cancer types, and tobacco-related indicators. Methods: This study analyzed real-world data from the five Regional Health Administrations of mainland Portugal from 2021 to 2023, focusing on tobacco abuse prevalence, tobacco-related cancer rates, and smoking-related consultations. Results: Tobacco abuse affects 11–16% of individuals in Portugal. A decline in tobacco abuse was observed in RHA “North” but not in other regions. The highest prevalence of tobacco-related cancers varied by region, with lung cancer most prevalent in RHA “North” and “Lisbon and Vale do Tejo” and colorectal cancer in RHA “Centre”. Tobacco abuse and related cancer rates generally increased over three years, except in RHA “North”. The proportion of smokers with documented habits and those receiving smoking-related consultations grew, particularly in RHA “North”, while smoking abstinence rates showed a progressive rise, with RHA “North” having the highest rates. Conclusions: The study highlights the need for further research on tobacco’s impact on cancer and addressing socioeconomic and healthcare access disparities for effective tobacco control.