1/. You can use lookup, even with multiple conditional expressions. The function wizard generates one pair only, but you can manually add as many as you like.
Cf. SAP Data Services Reference Guide, section 6.3.91 lookup:
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Syntax: lookup (<lookup_table>, <result_column>, <default_value>, <cache_spec>,<compare_column>, <expression>)
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and
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Note: You can specify more than one <compare_column> and <expression> pair—simply add additional pairs at the end of the function statement. The values must match for all specified pairs in order for the lookup function to find a matching row.
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2/. If your lookup is 6M records, use DEMAND_LOAD_CACHE.
3/. If you want to speed up your data flow processing, your only option would be to use a left outer join, pushed down to the database. If your data flow is complex, use a Data_Transfer transform to store the result of previous transformations in a temporary table in the same database as your lookup table. Don't use a lookup function anymore, but left-outer-join your temp table with the (lookup) table (using exactly the same conditions as you used in the lookup). If your target table is in the same database, too, the full logic will be puhed down to the database (and typically run much faster).
Cf. Let the database do the hard work! Better performance in SAP Data Services thanks to full SQL-Pushdown for more details on these techniques.