Mexico is considered a mega-diverse country due to its terrestrial, marine, and biological richness. Throughout history, Mexican medicinal plants have been used to elaborate decoctions, pastes, and powders to treat neoplastic, gastrointestinal, metabolic, neurodegenerative, skin, and infectious disorders. Cancer constitutes a group of diseases that result from the uncontrolled growth and proliferation of cells. Current treatment regimens against it encompass the administration of chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Despite their possible efficacy, their use is often related to the possibility of relapse, the development of serious adverse events, toxic effects, and many drug-resistance mechanisms. As an alternative, Mexican medicinal plants have been extensively studied using their capacity to elicit strong anticancer activities and possess novel bioactive and safe compounds. This review concentrates on the knowledge gained in recent years (2011–2022) about the anticancer properties of extracts and isolated compounds from Mexican medicinal plants. Generalities, antioxidant activities, features of cancer cells, and drug-resistance mechanisms are reviewed in this work. In addition, the possible anticancer mechanisms of isolated compounds and the status of FDA-approved cancer drugs derived from plants are covered. Finally, our perspective on the future of traditional medicine and Mexican medicinal plants in cancer treatment is presented.