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.
Bring sugar and water to a boil in a small saucepan and cook until sugar is dissolved. Let cool completely and then refrigerate until ready to use. Syrup will keep for up to 1 week stored in an airtight container in the refrigerator.