The article describes the theoretical, legal, and criminological issues of international cooperation of Kazakhstan, national models of some countries in the combat against drug trafficking, and the spread of drug use. The authors disclosed the basic concepts of structural elements of the mechanism for legal regulation of the combat against illicit trafficking in narcotic drugs, psychotropic substances and precursors in Kazakhstan, carried out the analysis of modern criminal and common law in terms of regulation of the methods of combating against illicit trafficking in narcotic drugs, psychotropic substances and precursors and related compounds of these types of crime, criminological characteristics of drug-related crimes across regions and areas of Kazakhstan. The result of the scientific research is the formulated theoretical propositions and recommendations for improving the current legislation of the Republic of Kazakhstan and its practical application.