Place equal parts chili powder and salt on a plate and mix to evenly combine. Rub a lime wedge around the edge of 2 margarita or martini glasses and then dip the glasses in the chili powder mixture to thinly coat the rim.
Fill a cocktail shaker with ice cubes. Add the lime juice, blood orange puree, mezcal, orange liqueur, and simple syrup. Shake vigorously for 10 seconds and then strain into each glass.