A fiery atmosphere is expected after the bragging rights shifted from Inter to their city neighbours last season.
Milan lifted their first Serie A title in 11 years in May to wrestle the trophy away from Inter, who finished second, two points adrift.
Lukaku, who had helped Inter capture the title in the previous campaign, returned to the club on loan from Chelsea, hoping to help them regain the crown but picked up a thigh injury ahead of their 3-1 home win over Cremonese.
Nevertheless, Tuesday's Lukaku-less win over the promoted side was a big boost to the team's morale after they hit their first bump in the road this season, a 3-1 defeat at Lazio last Friday.
"Inter arrive (to the derby) well, after an important match and a victory. We know it will be a delicate match for us and for the fans, we will try to prepare it in the best way possible," Inzaghi said.
Lautaro Martinez (25), the club's top scorer last season, has shown he can take on the burden of leading the line in the absence of Lukaku, having either scored or made an assist in each of Inter's first four games.
"It will be a very important match, we are focussed and on the right path, we want always to move forward," Martinez said.
In contrast, Milan seem to have lost their focus after failing to break down Sassuolo in a disappointing 0-0 away draw on Tuesday.
Inter are second in the table with nine points, a point behind leaders AS Roma while Milan have eight points, having also been held to a 1-1 draw at Atalanta last month.
Milan manager Stefano Pioli (56) has faith his side have learned their lessons and will not repeat the same mistakes as they made in midweek.
"The mentality of the team has stayed strong and self-aware, but we can play better on a technical level and when it comes to choices," he said.
"It is a derby, the rivalry is strong and we know... the weight the result can have and we will prepare for the match in the best way possible."
Juventus have also drawn two of their opening four games and face a crucial match at Fiorentina on Saturday.
Juve coach Massimiliano Allegri (55) will hope for a better performance than in Wednesday's 2-0 home win over Spezia when they failed to capitalise on a good start and needed a late second goal to make the points safe.
New signing Arkadiusz Milik (28) got his Juve career off to a good start with their second goal in stoppage time, minutes after coming off the bench to replace Dusan Vlahovic (22).
"He is important, he is a starting player because Vlahovic cannot play in all matches," Allegri said.
Table-toppers AS Roma are in high spirits and travel to Udinese on Sunday after Paulo Dybala (28) got off the mark in his fourth match at the club with two goals and a superb performance in their 3-0 win over Monza.
"Paulo is the kind of talent who plays with the team and for the team. We all know he was not born for the defensive stage, but he does a great job there too," manager Jose Mourinho said.
