Cocaine is the foundation of your empire and has been in short supply since your downfall. You start off by picking up the odd gram or so from the people you kill and making deals with Small Suppliers and selling them off to Dealers and Fronts, but that isn't really going to be enough. You have to move up and start making deals with Large Suppliers, who will sell you keys (kilograms) of coke for mass sums of money. However, you make more money than you lose, so it's always worth it – unless you blow the deal that is. Once you buy and secure keys of coke, you'll have to distribute to all your fronts via coke runs.
Leads
Early into the game, you'll make contact with Felix, an old acquaintance of yours. He'll be helping you out by supplying leads—possible contacts for obtaining coke—that you can follow in the Sat Phone menu. Each lead comprises a side mission of some sort. You can be tasked with doing a variety of things, sometimes more than one at a time:
- Locating and killing one or more individuals.
- Defending a particular individual from an ambush (Note: sometimes, you'll be defending yourself).
- Driving around in a designated car and possibly making pickups or deliveries.
- Muscling an individual: injuring him to the point of surrender without killing him.
Complete the mission successfully, and you'll gain money and sometimes some Turf. Most importantly, though, you'll have access to a Supplier mission. You'll start out getting leads on Small Suppliers until you take over Little Havana and gain a Storehouse. Then you'll start getting leads on Large Suppliers.
Once you go to the Islands and meet the Sandman, he will provide leads you can follow while you're there. These in turn unlock Large Supplier missions elsewhere on the Islands.
Once you complete a Lead mission, be sure to follow through with the Supplier mission. It will not remain available for long.
Dealers
Anytime you have loose grams of coke on your person, you can seek out a Dealer (a white dot on the map) and negotiate a sale (using the meter). The disadvantage is that you can only sell off 100g at a time, but the advantage is that Dealers can usually afford a better rate for your coke (up to $100 per gram, meaning up to $10,000 per deal).
Fronts
Any front you have already purchased will be more than happy to take any loose grams you possess off your hands. Simply approach the associate for that front and the option will be presented. Using the Phone menu, you can inspect the current demand for any front you own, represented as dollars per gram. The Front will buy your coke from you at that rate. Note, though, that many places won't offer the same rates as Dealers (though some like the Babylon Club pay off better than others), that they will buy all the grams you possess, and that selling to a front reduces demand for that area, which can affect profits for later sales and Distribution Runs.
Coke runs
After you gain a storehouse, you'll be able to do coke runs and the first one will be waiting for you in your storehouse for you to practice. After that, you have to resupply the storehouse.
To unlock a coke deal, you have to press 
, then select Empire, then Business and select one of the leads, complete this mission, and providing your gang heat isn't too high, you'll get a Large Supplier deal. Go meet with the dealer and negotiate the price for how many grams using the normal meter method. Now comes the hard part. You have to transport it to your storehouse in one of your exotic cars, all the while dodging attacks from gangs. Once you reach the open garage, your coke is unloaded and the transport run is complete.
After you've done this, you'll be able to go on the Miami Distribution mission where you give out coke to all your fronts. This is where you make the big money and the only way you'll get those expensive exotics. Other gangs won't be happy with this however, and they'll come after you in cars and even attack your fronts forcing you to defend them. Once you've collected your money, head to a bank to end the mission.
After you've been invited to the Islands and made a deal with "The Sandman", you'll be able to get even larger shipments from the islands. It sounds great, however there is a catch. You still need to psychically transport the coke to one of your storehouses: this time using one of your boats. On the island side, you'll have pirates trying to kill you and on the Miami side you'll have the Coast Guard trying to kill you, so it can be pretty tough. However it's worth the effort, as larger shipments means more money from each front. Each storehouse has a water-based goal marker your boat can reach, and once you leave the Islands, you can choose where in Miami you enter, so you can pick the spot closest to your desired storehouse.
At the very end of the game and after you've "bought" the plantation from "The Sandman", you can go to any storehouse and start a Miami Distribution mission with a full 30 keys of coke, all for $500,000. No more hassle.
Tips
Save before attempting every mission
This is simple advice really – theres is a lot of money at stake and a lot of things can go wrong, so saving beforehand means you can just quit and go back without being annoyed that you're losing all your hard effort.
Keep your heat meters low
This cannot be stressed enough; the higher your heat is, the more gangs will come after you and attack your fronts. Each front you visit will increase your gang heat, so it can't be completely avoided, but make the start as easy as possible for yourself. The same goes for cop heat. The last thing you need is to be defending one of your fronts and then they turn up and you have to run away from them causing damage to your car. You can't decrease Gang or Cop heat in missions, so don't even try. Pay them down once the run's over.
Vehicles
Choose a car that's both fast and has good amour. At the start you wont have them, but the Stampede and Bodog Stampede are good choices. If you can handle a faster car, it can be do in the Rattler, however in a Stampede you'll have more room for damage. Drive carefully but fast; if you've got the whole of Miami to cover, then that car is going to take a hell of a beating so try to not bump into things. Get used to the route you're going to take and make sure it's the best one. You can't repair cars in the mission so don't even try. And don't get out of the car while the mission is in progress. If you're defending a front, attack from inside the car. If you get out, you only have a short time to get back in before the mission fails.
Fronts
If you can afford it, buy some time for your fronts by investing in cameras and henchmen for them. Once a front is under attack, the cameras delay the initial assault while the henchmen help to hold the front once it actually starts. If you can make it to the front and kill off the attackers, you preserve the front and will be able to collect the money from it.
Defending fronts that aren't too far away is worthwhile since you'll be able to collect the money from it. But if a front is being attacked on the other side of Miami, just leave it. There's no point rushing over there, causing damage to your car, and then you might not even make it. Then you'd have to go back to those fronts you missed. Use it instead as an opportunity: when a front is being attacked, rarely are you spotted by a rival gang, meaning you can collect money in peace.
Make it a point after each run to repair those fronts that were damaged; you'll still make a profit, provided you weren't completely useless. Plus a front must be fully repaired at the start of a Distribution run in order to participate.
Afterward
Make the most use of your illicit gains. Buy any exotics you want, repair any damaged fronts, and pay off Vice before laundering your money at the bank; this will reduce their cut. You can end distribution missions any time you want simply by going to any bank (each bank will have a goal marker); if you don't think you're going to make it then quit before you lose all that cash. Despite that, fortune favors the bold; if you can hit all your fronts and complete the coverage then the demand will increase for next time which means more money.