Small ubiquitin-like modifiers (SUMOs) mediate a variety of cellular functions of protein targets mainly in the nucleus but in other cellular compartments as well, and thereby participate in maintaining cellular homeostasis. SUMO system plays important roles in transcriptional regulation, DNA damage responses, maintaining genome integrity, and signaling pathways. Thus, in some cases, loss of regulated control on SUMOylation/deSUMOylation processes causes a defect in maintaining homeostasis and hence gives a cue to cancer development and progression. Furthermore, recent studies have revealed that SUMO system is involved in cancer metastasis. In this review, we will summarize the possible role of SUMO system in cancer development, progression, and metastasis and discuss future directions.