Preponderant experimental and clinical evidence has demonstrated that pervasive cancer cell heterogeneity in both phenotypic presentations and functional properties exists, such that a population of cancer cells with cardinal stem cell properties (i.e., cancer stem cells) pre-exists in untreated tumors and spatiotemporally evolves during tumor progression and therapeutic interventions. Recent studies have also revealed significant phenotypic and functional plasticity in cancer cells, regulated by both genetic networks and epigenetic mechanisms. Both cancer cell heterogeneity and plasticity constitute major barriers to efficient and durable clinical treatments. Ever since the revival of the cancer stem cell research field around the turn of the century, we have made great strides in identifying and elucidating the biology of cancer stem cells in virtually all tumor systems. Significant progress has also been made in understanding how cancer stem cells interact with the cellular constituents and soluble factors in the proinflammatory and immune-suppressive tumor microenvironment. Facilitated by an explosion of technical advances in recent years, especially single-cell RNA-seq, we are achieving an unprecedented appreciation of the complexity of the cellular heterogeneity of human tumors. Significantly, novel therapeutic strategies that target cancer stem cells and cancer cell heterogeneity and plasticity are rapidly progressing to the clinical arena. This conference is organized to recapitulate these recent advances in our understanding of cancer stem cell biology and, importantly, the clinical translation of targeting cancer stem cells.