Cancer is one of the leading global causes of death, responsible for nearly ten million deaths in 2021, with its burden rising largely due to increased life expectancy. Major contributors include preventable lifestyle factors, especially tobacco use, obesity, unhealthy diet, and physical inactivity, alongside infections, environmental exposures, and chronic comorbidities. Global disparities are pronounced: while incidence and mortality decline in high Human Development Index countries due to prevention, screening, and treatment, low Human Development Index countries experience rising mortality driven by limited healthcare access. Cancer develops through a sequence of transitions that typically begin with an initiating event, such as a genetic mutation, viral infection, or altered cellular state, followed by the accumulation of driver mutations and epigenetic changes. Tumor evolution involves interactions with the microenvironment, inflammation, metabolic dysfunction, and aging-associated processes such as senescence. Multiple theoretical models, including somatic mutation, tissue organization, and systems-level ground state frameworks, highlight that carcinogenesis results not only from genetic alterations but also from disruptions in tissue organization. Risk arises from inherited germline variants, replication-associated random mutations, and environmental factors. Additional modifiers include microbiome composition, metabolic disease, chronic inflammation, and postzygotic mosaic mutations, which are early prenatal mutations that populate subsets of tissues and may shape lifelong cancer susceptibility. Overall, cancer is best understood as a systemic, multifactorial disease emerging from the convergence of biological aging, environment, lifestyle, and genetic variation.