Phytochemicals are plant-derived secondary metabolites, which may exert many biological activities in humans, including anticancer properties. Although recent findings appear to support their role in cancer prevention and treatment, this issue is still controversial. Anti-cancer activity of phytochemicals mainly depends on their multi-target mechanism of action, including antimutagenic, antioxidant and antiproliferative activities. Furthermore, they may modulate the host immune response to cancer, reducing inflammatory microenvironment and enhancing lymphocyte onco-surveillance. Since carcinogenesis is multi-factorial and involves several signaling pathways, multi-targeted agents as phytochemicals may represent promising anticancer compounds. This narrative review aims to analyze the current literature on phytochemicals highlighting their specific targets on carcinogenic molecular pathways and their chemopreventive role. A full comprehension of their activity at molecular and cellular levels will contribute for a better understanding of phytochemical clinical efficacy, thus promoting the identification of new effective plant-derived therapeutics.