First things first, there are a number of problems to killing Deadpool. His healing factor, Death's infatuation with him, Thanos's curse, all of it makes him completely unkillable. See, the whole "Death won't let him die" is inaccurate: She wants him to die just as much as Deadpool WANTS to die. As long as Deadpool lives, they can't be together. That's WHY Deadpool wants to die: So he can be with his love. Thanos cursed him with immortality to keep Wade from her, leaving the way open to Thanos. So, if we want to kill Wade, we need to get rid of the curse, then we can kill Deadpool. That bit's easy, it's the curse that's tricky. Perhaps Doctor Strange could help us. The good Doctor's hippocratic oath would generally be an obstacle to this, but I think we can convince him that Deadpool's insanity and perpetual agony as he's torn apart time and time again in search of death is no life worth living.
So Doctor Strange can perhaps aid us in alleviating the curse, provided he's at his best. Magic is so finicky we can't really explore beyond that point without further elaboration on what Thanos did. But presuming we remove the curse, getting around Deadpool's healing factor is easy.
See, during his Reign, Norman Osborn did a great deal. One of his lesser achievements? He cured cancer. Why? To kill Deadpool. See, Deadpool's cancer is constantly active, spreading at the exact same rate his healing factor is fighting it. Realizing this, Osborn put together a cure for cancer, then weaponized it. Firing this into Wade would cure his cancer. This is bad because his healing factor considers the cancer part of 'baseline' Wade, i.e., Wade had all his limbs when he got his healing factor, so said healing factor regenerates those. Hence why it can't cure his scars. However, cancer can't be regenerated because it's a disease. So take out the cancer, and the healing factor goes nuts looking for anything that COULD be cancer, trying to cure it. So any impurities in Wade's body will be hunted down, and eliminated. Again, this is bad because these are ALL part of baseline Wade. The more the healing factor looks for cancer to eliminate, the more parts of normal Wade will be destroyed, and the crazier it'll go.
Until, eventually, Wade falls apart, melts into goo, whatever, dude dies.
We inform Doctor Strange to look back through time at that incident, when Norman was designing the cure, and we should be able to replicate it, by taking it to Reed Richards. Generally, getting an appointment with the Fantastic Four is tricky, but tell them we know how to cure cancer, but lack the means to design it, and that should get their attention. We get the cure, they begin mass distributing it, we take it to Wade, tell him that we know how to kill him, and give it to him. Chances are pretty good he uses it on himself.
Death rejoices, Wade and her go on their honeymoon to the DC Universe so Death can introduce him to his new family: The Endless.
In summary: We've killed Wade Wilson AND cured cancer. I'd say that's a mission accomplished.
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