Although the tumor microenvironment is well known to be important for cancer progression, understanding how the complex molecular networks contribute to cancers, particularly with all the different types of cancers, remains a limitation that often prevents the successful translation of research results in effective clinical applications. One approach has been the use of RNAi therapeutics. The exciting potential of these therapies is currently hampered by the high risk of off-target effects due to the imperfect complementarity used by these noncoding RNAs (ncRNAs) to recognize their mRNA targets. While this suggests that the miRNA analog specificity is one problem, another major obstacle is the problem of developing effective and targeted delivery systems specifically for the tumor that avoids serious adverse complications. These roadblocks indicate the need for the development of novel miRNA delivery systems and target-specific miRNA analogs before successful miRNA anticancer therapies become available. In this chapter, we discuss the current limitations of various types of miRNA analogs and the variety of delivery systems that are currently being developed.