I'd guess it should have a significant impact and hopefully would make enough difference to slowly erode their power, but I think they already have fairly significant non-drug income and could likely increase that in various ways. In addition to what others mention, they engage in illegal mining, logging, and poaching and likely have substantial export income (this may be new in the past couple of decades and it is obviously hard to tell how extensive it is and how connected the people engaging in those activities are to the cartels involved in the drug trade). They kidnap for labor as well as extortion and can make use of slave labor as long as they control territory. Even if drugs are legalized they will likely keep a small part of that market based on price, convenience, and in some cases violence towards current customers who try to switch to legal supply. It at least seems like the earlier the US legalizes drugs the better chance that it will have a large impact on the cartels.

Most of the reporting I've seen attributes this wider focus to the splintering of cartels due to the recent Mexican drug war that started after Vincente Fox was elected to be the first non-PRI president in almost a century. While that didn't end collusion it did end the stable relationships the PRI had with particular cartels (research has looked at this on the state level and found that the level of volence correlates with when a state elected non-PRI government). Calderon greatly expanded this conflict and either started or expanded the policy of going after the heads of the cartels in the hopes that arresting or killing them would cause the cartels to collapse. Instead, it caused them to splinter with different groups both incresingly violent in competition with each other as well as looking for new sources of income. It seems like AMLO is trying to return to the old PRI model of unofficially recognizing particular cartels as controlling particular areas (or nearly officially in the Sinaloa Cartel case), but so far it doesn't seem to have changed much.