Cancer will remain a global major health problem unless new diagnostic, prognostic, and management approaches are discovered to address both loss of life and quality of life. Here we summarize the general physiology, pathology, heterogeneity, and evolution of cancer, current status, limitations and challenges associated with prevention, incidence, treatment, survival, and mortality, as well as future directions with regards to solid tumors. Perspectives are provided on how to improve pre-clinical understandings, outcomes, and patient care. Further, this comprehensive, timely overview of the literature has educational value as part of an academic course, seminar, or as a supplementary text.